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1.
Rev. cuba. med. mil ; 51(2): e1566, abr.-jun. 2022.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1408828

ABSTRACT

RESUMEN Introducción: El trastorno por estrés postraumático afectan la salud mental de los pacientes pediátricos, se considera muy común en estos pacientes. Estudios científicos apoyados en la resonancia magnética han fundamentado una estrecha relación entre el estrés postraumático y cambios estructurales en el cerebro. Se realizó una revisión bibliográfica en el periodo de abril a mayo de 2021, en los recursos disponibles en MEDLINE, SciELO, Pubmed y Elsevier. Del total de consultas se citaron 25 referencias. Objetivo: Describir los signos radiológicos en la neuroimagen de pacientes pediátricos con estrés postraumático. Desarrollo: Los estudios de neuroimagen en niños y adolescentes con trastorno por estrés postraumático se han centrado en estructuras anormales y la funcionalidad de algunas regiones individuales del cerebro; estas implican las regiones cerebrales asociadas con la fisiopatología, ellas son: la corteza prefrontal medial y dorsolateral; la corteza orbitofrontal; ínsula; núcleo lentiforme; amígdala; hipocampo y el parahipocampo; la corteza cingulada anterior y posterior; el precúneo; cúneo; el giro fusiforme y lingual y los tractos de materia blanca que conectan estas regiones cerebrales. Conclusiones: Los signos radiológicos en la neuroimagen de pacientes pediátricos con trastorno por estrés postraumático son: reducción de los volúmenes del hipocampo; del volumen cerebral e intracraneal y del volumen de la amígdala, así como una disminución del área total del cuerpo calloso. Además se observa que el volumen hipofisario y los volúmenes de materia gris cerebral fueron menores en los pacientes con estrés postraumático.


ABSTRACT Introduction: Post-traumatic stress disorder affects the mental health of pediatric patients; it is considered very common in these patients. Scientific studies supported by magnetic resonance imaging have established a close relationship between post-traumatic stress and structural changes in the brain. A bibliographic review was carried out in the period from April to May 2021, in the resources available in MEDLINE, SciELO, Pubmed and Elsevier. Of the total of consultations, 25 references were cited. Objective: To describe the radiological signs in the neuroimaging of pediatric patients with post-traumatic stress disorder. Development: Neuroimaging studies in children and adolescents with post-traumatic stress disorder have focused on abnormal structures and the functionality of some individual brain regions; these involve the brain regions associated with pathophysiology, they are: the medial and dorsolateral prefrontal cortex; the orbitofrontal cortex; insula; lentiform nucleus; amygdala; hippocampus and parahippocampus; the anterior and posterior cingulate cortex; the precuneus; cuneus; the fusiform and lingual gyrus and the white matter tracts that connect these brain regions. Conclusions: The radiological signs in the neuroimaging of pediatric patients with post-traumatic stress disorder are: reduction of the volumes of the hippocampus; brain and intracranial volume and amygdala volume, as well as a decrease in the total area of ​​the corpus callosum. In addition, it is observed that the pituitary volume and the volumes of cerebral gray matter were lower in patients with post-traumatic stress.

2.
Biomédica (Bogotá) ; 42(1): 196-206, ene.-mar. 2022. graf
Article in Spanish | LILACS | ID: biblio-1374518

ABSTRACT

Introducción. Las lesiones del nervio facial afectan la plasticidad a largo plazo en el hipocampo, así como la memoria de reconocimiento de objetos y la memoria espacial, dos procesos dependientes de esta estructura. Si bien se ha descrito una activación de la microglía en la corteza motora primaria asociada con esta lesión, no se conoce si ocurre algo similar en el hipocampo. Objetivo. Caracterizar en ratas el efecto de la lesión unilateral del nervio facial sobre la activación de células de la microglía en el hipocampo contralateral. Materiales y métodos. Se hicieron experimentos de inmunohistoquímica para detectar células de la microglía en el hipocampo de ratas sometidas a lesión irreversible del nervio facial. Los animales se sacrificaron en distintos momentos después de la lesión, para evaluar la evolución de la proliferación (densidad de células) y la activación (área celular) de la microglía en el tejido del hipocampo. Los tejidos cerebrales de los animales de control se compararon con los de animales lesionados sacrificados en los días 1,3, 7, 21 y 35 después de la lesión. Resultados. Las células de la microglía en el hipocampo de animales con lesión del nervio facial mostraron signos de proliferación y activación a los 3, 7 y 21 días después de la lesión. Sin embargo, al cabo de cinco semanas, estas modificaciones se revirtieron, a pesar de que no hubo recuperación funcional de la parálisis facial. Conclusiones. La lesión irreversible del nervio facial produce proliferación y activación temprana y transitoria de las células de la microglía en el hipocampo. Estos cambios podrían estar asociados con las modificaciones electrofisiológicas y las alteraciones comportamentales dependientes del hipocampo descritas recientemente.


Introduction: Facial nerve injury induces changes in hippocampal long-term synaptic plasticity and affects both object recognition memory and spatial memory consolidation (i.e., hippocampus-dependent tasks). Although facial nerve injury-associated microglíal activation has been described regarding the primary motor cortex, it has not been ascertained whether something similar occurs in the hippocampus. Peripheral nerve injury- associated microglíal changes in hippocampal tissue could explain neuronal changes in the contralateral hippocampus. Objective: To characterize the effect of unilateral facial nerve injury on microglíal proliferation and activation in the contralateral hippocampus. Materials and methods: Immunohistochemical experiments detected microglíal cells in the hippocampal tissue of rats that had undergone facial nerve injury. The animals were sacrificed at specific times after injury to evaluate hippocampal microglíal cell proliferation (cell density) and activation (cell area); sham-operated animals were compared to lesioned animals sacrificed 1,3, 7, 21, or 35 days after injury. Results: Facial nerve-injured rats' hippocampal microglíal cells proliferated and adopted an activated phenotype 3- to 21-days post-lesion. Such modifications were transient since the microglíal cells returned to their resting state five weeks after injury, despite the injury's irreversible nature. Conclusions: Facial nerve injury causes the transient proliferation and activation of microglíal cells in the hippocampus. This finding might partly explain the morphological and electrophysiological changes described for CA1 pyramidal neurons and the impairment of spatial memory consolidation which has previously been observed in facial nerve-injured rats.


Subject(s)
Facial Nerve , Hippocampus , Rats , Immunohistochemistry
3.
Article in Chinese | WPRIM | ID: wpr-936110

ABSTRACT

OBJECTIVE@#To investigate the influence of chronic masseter hyperalgesia induced by 17β-estradiol (E2) and experimental occlusal interference (EOI) on underlying mechanism in hippocampus of ovariectomized (OVX) rats.@*METHODS@#In the study, 32 OVX rats were randomly divided into 4 groups (8 rats/group): The control group was OVX group, and 0 μg/d E2 (vehicle) injection was started 7 d after OVX without EOI; in the experimental group (1) OVX + E2 group, 80 μg/d E2 injection was started 7 d after OVX without EOI; in the experimental group (2) OVX + EOI group, vehicle injection was started 7 d after OVX and EOI was applied 17 d after OVX; in the experimental group (3) OVX + E2 + EOI group, 80 μg/d E2 injection was started 7 d after OVX and EOI was applied 17 d after OVX. Bilateral masseter muscle mechanical withdrawal thresholds were measured before OVX, 7 days after OVX (before E2 injection), 17 days after OVX (10 days after E2 injection and before EOI) and 24 days after OVX (7 days after EOI). Immunofluorescence staining was used to reveal phospho-extracellular signal regulated kinase 1/2 (p-ERK1/2)-positive neurons in CA3 of hippocampus. The protein expression of p-ERK1/2 in hippocampus was detected using Western Blot.@*RESULTS@#Compared with the control group [left side: (135.3±8.5) g, right side: (135.4±10.8) g], bilateral masseter muscle mechanical withdrawal thresholds of OVX+E2 group [left side: (113.3±5.6) g, right side: (112.5 ± 5.6) g] and OVX+EOI group [left side: (93.3±5.4) g, right side: 90.8±5.5) g] were decreased (P < 0.01). Bilateral masseter muscle mechanical withdrawal thresholds were significantly lower in OVX+E2+EOI group [left side: (81.2±6.2) g, right side: 79.8±7.7) g] than in the control, OVX+E2 and OVX+EOI groups (P < 0.05). The proportion of p-ERK1/2 positive neurons in the CA3 region of the hippocampus was increased in the control, OVX+E2, OVX+EOI and OVX+E2+EOI groups in turn, and the difference between the groups was statistically significant (P < 0.05). p-ERK1/2 protein expression was increased in the control, OVX+E2 and OVX+EOI groups in turn, but the difference was not statistically significant (P>0.05). p-ERK1/2 expression was significantly higher in OVX+E2+EOI group than in the other three groups (P < 0.05).@*CONCLUSION@#High concentration of E2 could exacerbated EOI-induced chronic masseter hyperalgesia in ovariectomized rats, and its central mechanism may be related to the upregulation of the phosphorylation of ERK1/2 in hippocampus.


Subject(s)
Animals , Estradiol , Female , Hippocampus , Humans , Hyperalgesia/chemically induced , Masseter Muscle , Ovariectomy , Rats , Rats, Sprague-Dawley
4.
Neuroscience Bulletin ; (6): 474-488, 2022.
Article in English | WPRIM | ID: wpr-929086

ABSTRACT

Astrocytes are increasingly recognized to play an active role in learning and memory, but whether neural inputs can trigger event-specific astrocytic Ca2+ dynamics in real time to participate in working memory remains unclear due to the difficulties in directly monitoring astrocytic Ca2+ dynamics in animals performing tasks. Here, using fiber photometry, we showed that population astrocytic Ca2+ dynamics in the hippocampus were gated by sensory inputs (centered at the turning point of the T-maze) and modified by the reward delivery during the encoding and retrieval phases. Notably, there was a strong inter-locked and antagonistic relationship between the astrocytic and neuronal Ca2+ dynamics with a 3-s phase difference. Furthermore, there was a robust synchronization of astrocytic Ca2+ at the population level among the hippocampus, medial prefrontal cortex, and striatum. The inter-locked, bidirectional communication between astrocytes and neurons at the population level may contribute to the modulation of information processing in working memory.


Subject(s)
Animals , Astrocytes , Hippocampus/physiology , Humans , Memory, Short-Term/physiology , Mice , Neurons/physiology , Population Dynamics
5.
Article in Chinese | WPRIM | ID: wpr-935769

ABSTRACT

Objective: To investigate the effect and underlying mechanism of paeoniflorin on hippocampal neuron apoptosis induced by lead acetate. Methods: In September 2020, primary hippocampal neuronal cells were isolated and cultured from fetal rats, and identified using cellular immunofluorescent. MTT assay was used to measure the cell viability to determine the concentration and time of lead acetate-induced hippocampal neuron apoptosis. MTT was also used to evaluate the effect of paeoniflorin concentration on the apoptosis of hippocampal neurons induced by lead acetate. According to the results, different concentrations of paeoniflorin were selected to intervene hippocampal neuron cells, after 24 h, lead acetate was added to the cells, meanwhile, blank and model groups were set up, the content of reactive oxygen species (ROS) , superoxide dismutase (SOD) , lactate dehydrogenase (LDH) , malondialdehyde (MDA) and Caspase-3 were measured. Extracellular signal regulated kinase (ERK) , phosphorylated ERK (p-ERK) , p38 mitogen -activated protein kinases (p38MAPK) , phosphorylated p38MAPK (p-p38MAPK) , c-Jun N-terminal kinase (JNK) and phosphorylated JNK (p-JNK) protein expression in hippocampal neuronal cells were determined by Western blotting. Results: The isolated and cultured hippocampal neurons were identified by immunofluorescence chemical staining and then treated with lead acetate, MTT results showed that lead acetate had the best toxicity effect when treated for 24 h at a concentration of 25 μmol/L. Paeoniflorin showed no cytotoxic effect on hippocampal neuronal cells when the concentrations below 80 μmol/L. Compared with the model group, the activity of hippocampal neuronal cells was significantly increased after treating with 20, 40 or 80 μmol/L paeoniflorin (P<0.05) . Compared with the blank group, the ROS activity, LDH release level, MDA content and caspase-3 content were significantly increased (P<0.01) , and the SOD activity was significantly decreased (P< 0.01) in the hippocampal neuronal cells of the model group. Compared with the model group, the ROS activity, LDH release level, MDA content and caspase-3 content were obviously decreased (P<0.05) , SOD activity was significantly increased (P <0.01) after hippocampal neuronal cells were treated with 40 or 80 μmol/L paeoniflorin. Relative to the model group, the ratio of p-ERK/ERK were significantly up-regulated (P<0.01) , while the ratios of p-p38MAPK/p38MAPK and p-JNK/JNK were significantly down-regulated after hippocampal neuronal cells were treated with 40 or 80 μmol/L paeoniflorin (P<0.05) . Conclusion: Paeoniflorin may down-regulate the expression of p-p38MAPK and p-JNK protein, up-regulate the expression of p-ERK protein, and inhibit the apoptosis of hippocampal neurons induced by lead acetate through the MAPK signaling pathway.


Subject(s)
Acetates/pharmacology , Animals , Apoptosis , Caspase 3/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Glucosides , Hippocampus/metabolism , JNK Mitogen-Activated Protein Kinases/pharmacology , Lead , Monoterpenes , Neurons/metabolism , Rats , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
6.
Article in Chinese | WPRIM | ID: wpr-933294

ABSTRACT

Objective:To evaluate the effect of long-term intake of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) on the activation of hippocampal microglia in a mouse model of postoperative cognitive dysfunction (POCD).Methods:Ninety-six clean-grade healthy male C57BL/6 mice, aged 8 weeks, weighing 18-24 g, were stratified according to body weight and divided into 4 groups ( n=24 each) by a random number table method: control diet group (group C), ω-3 PUFAs group (group ω), control diet plus POCD group (group C+ P) and ω-3 PUFAs plus POCD group (group ω+ P). Mice were fed a special ω-3 PUFAs diet (DHA 0.14 g/100 g, EPA 0.03 g/100 g) for 12 weeks in group ω and group ω+ P, while mice were fed with a control diet for 12 weeks in group C and group C+ P.Tibial fracture procedures were performed under isoflurane anesthesia to develop the POCD model after 12 weeks of feeding.The fear conditioning test and Y maze test were performed on 1st and 3rd days after developing the model.The mice were sacrificed after behavioral tests, and the hippocampal tissues were removed for determination of the contents of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) (by gas chromatography-mass spectroscopy), density of Iba-1 positive microglia (by immunofluorescence staining), and expression of mature brain-derived neurotrophic factor (mBDNF) and precursor brain-derived neurotrophic factor (pro-BDNF) (by Western blot), and contents of interleukin-1beta (IL-1β) and interleukin-6 (IL-6) (by enzyme-linked immunosorbent assay). Results:Compared with group C, the contents of DHA and EPA were significantly increased, the percentage of freezing time in the contextual test was increased, mBDNF/pro-BDNF ratio was increased ( P<0.05), no significant change was found in the rotation accuracy in Y maze test, density of Iba-1 positive microglia and contents of IL-1β and IL-6 in hippocampus ( P>0.05) in group ω ( P<0.05), and no significant change was found in the contents of DHA and EPA ( P>0.05), the percentage of freezing time in the contextual test and accuracy of rotation in Y maze test were decreased on 1st and 3rd days after operation, the density of Iba-1 positive microglia and contents of IL-1β and IL-6 were increased, and mBDNF/pro-BDNF ratio was decreased in group C+ P ( P<0.05). Compared with group C+ P, the contents of DHA and EPA were significantly increased, the percentage of freezing time in the contextual test and accuracy of rotation in Y maze test were increased on 1st and 3rd days after operation, the density of Iba-1 positive microglia and contents of IL-1β and IL-6 were decreased, and mBDNF/pro-BDNF ratio was increased in group ω+ P ( P<0.05). Conclusions:Long-term intake of ω-3 PUFAs can improve cognitive function in a mouse model of POCD, and the mechanism may be related to inhibition of activation of hippocampal microglia, reduction of inflammatory responses, and thus increasing the mBDNF/Pro-BDNF ratio.

7.
Article in Chinese | WPRIM | ID: wpr-931909

ABSTRACT

Objective:To investigate the effect and mechanism of non-selective histone deacetylase (HDAC) inhibitor sodium butyrate (NaB) on neuropathic pain and pain-induced memory impairment in mice.Methods:Forty clean grade male C57BL/6J mice were were divided into 4 groups by random number table method ( n=10 in each group): sham + saline, sham + NaB, chronic constriction injury (CCI)+ saline and CCI + NaB.The mouse CCI model was established by sciatic nerve ligation. Non-selective HDAC inhibitors NaB(300 mg/kg) was intraperitoneally injected into the mice in Sham+ NaB group and CCI+ NaB group once a day 15-28 days after modeling, while the mice in Sham+ saline group and CCI+ saline group were intraperitoneally injected with the same volume of saline. On the 14th and 28th day after operation, the athletic ability was measured by open field test (OFT), the pain behavior was measured by paw withdrawal threshold (PWT) and paw withdrawal latency (PWL), and the memory function was measured by Y-maze. After the behavioral experiment, hippocampus and spinal dorsal horn tissues were taken for the activity of HDAC measurement, and hippocampus tissues were taken for the expression levels of BDNF and PSD95 measurement. SPSS 25.0 software was used for statistical analysis. The data were compared by repeated measurement ANOVA and one-way ANOVA. Results:After treatment with NaB, the interaction effects of the accuracy of spontaneous alternation of PWT, PWL and Y maze in mice were significant( F=21.07, 6.98, 7.79, all P<0.05). Compared with the Sham + saline group, the PWT((0.83±0.30)g, (0.25±0.22)g, (0.24±0.11)g; both P<0.05), the PWL((14.97±4.02)s, (5.99±1.51)s, (6.87±0.90)s; both P<0.05) and the spontaneous alternation in Y maze(71.57±2.80)%, (56.96±0.60)%, (62.86±4.94)%; both P<0.05) in CCI+ Saline group and CCI+ NaB group were lower. After treatment with NaB, compared with CCI + saline group, PWT((0.22±0.13)g, (0.62±0.23)g; P<0.05), PWL((5.62±2.00)s, (8.82±2.13)s; P<0.05)and the accuracy of spontaneous alternation of Y maze were significantly higher ((56.54±7.50)%, (66.35±8.20)%; P<0.05), the HDAC activity in hippocampus((173.40±7.38)%, (122.70±8.40)%; P<0.05)and in spinal cord ((153.40±10.58)%, (111.40±11.40)%; P<0.05)were significantly lower, and the expression of BDNF((0.65±0.06), (0.87±0.43); P<0.05)and PSD95((0.70±0.40), (0.87±0.04); P<0.05)were significantly higher in CCI + NaB group. Conclusion:NaB can improve neuropathic pain and pain-induced memory impairment.The mechanism may be related to the inhibition of HDAC activity and the up-regulation of BDNF and PSD95 expression in hippocampus.

8.
Article in Chinese | WPRIM | ID: wpr-931908

ABSTRACT

Objective:To investigate the effects of early sleep deprivation(SD) on depressive-like behavior and hippocampus synaptic plasticity in adult mice with chronic unpredictable mild stress(CUMS) model.Methods:Thirty 2-week-old clean grade male mice were randomly divided into control group (CON group), CUMS group and SD + CUMS group according to the random number table, with 10 mice in each group. The mice in SD + CUMS group were subjected with sleep deprivation for 4 hours once a day during puberty (3 ~ 6 weeks old), and then were stimulated by CUMS after adulthood (9 weeks old). The mice in CUMS group were subjected with CUMS at the age of 9 weeks. And the mice in CON group were not given any intervention.The depressive-like behavior was evaluated by body weight, sugar water preference, tail suspension test and forced swimming test.The density of dendritic spines of basal and apical neurons in hippocampal CA1 was measured by Golgi staining, the frequency and amplitude of miniature excitatory postsynaptic current(mEPSC) of pyramidal neurons in the hippocampal CA1 region of mice were measured by electro-physiological patch clamp technique.Graphpad prism 7.0 software was used for statistical analysis and mapping. One-way ANOVA was used for comparison among multiple groups, and Tukey test was used for further pairwise comparison.Results:(1) After stress modeling, there were significant differences in body weight, sugar water preference percentage, forced swimming immobility time and tail suspension time among the three groups ( F=71.63, 39.82, 44.13, 43.07, all P<0.01). Compared with CON group, the mice in CUMS group and SD+ CUMS group had lower body weight ((25.51±0.37) g, (22.92±0.31) g, (20.12±0.27) g, both P<0.01), lower sugar water percentage preference ((87.40±1.65) %, (63.42±3.33) %, (49.68±3.70)%, both P<0.01), longer immobile time of forced swimming ((34.30±5.32) s, (119.20±12.03) s, (153.80±9.17) s, both P<0.01) and longer immobile time of tail suspension test((115.20±8.19)s, (156.80±4.35) s, (192.00±4.12) s, both P<0.01). Compared with CUMS group, SD+ CUMS group had lower body weight ( P<0.01), lower sugar water preference percentage ( P<0.05), longer immobile time in forced swimming test( P<0.05) and longer immobile time in tail suspension test( P<0.01). (2) Golgi staining results showed that the densities of dendritic spines of apical neurons and basal neurons in hippocampal CA1 area of the three groups were significantly different ( F=38.41, 41.34, both P<0.01). The densities of dendritic spines of basal and apical hippocampal neurons in CUMS group and SD+ CUMS group were lower than those in CON group ((7.74±0.22)/10 μm, (6.58±0.27)/10 μm, (5.00±0.13)/10 μm, both P<0.01), ((8.90±0.23)/10 μm, (7.63±0.30)/10 μm, (6.01±0.14)/10 μm, both P<0.01). Compared with CUMS group, the mice in SD+ CUMS group had lower densities of dendritic spines of basal and apical hippocampal neurons(both P<0.01). (3) Electrophysiological results showed that there were significant differences in the frequency and amplitude of mEPSC in hippocampal pyramidal neurons of the three groups ( F=38.90, 63.37, both P<0.01). Compared with CON group, the frequency and amplitude of mEPSC in pyramidal neurons of CA1 in CUMS group and SD+ CUMS group were significantly lower ((0.39±0.03)Hz, (0.20±0.02)Hz, (0.07±0.02)Hz, both P<0.01; (9.98±0.31)pA, (7.74±0.21)pA, 6.36±0.13)pA, both P<0.01). Compared with CUMS group, the frequency and amplitude of mEPSC in SD+ CUMS group were lower (both P<0.01). Conclusion:Adolescent sleep deprivation aggravates depressive behavior and hippocampus synaptic plasticity impairment in adult CUMS model mice.

9.
Article in Chinese | WPRIM | ID: wpr-931893

ABSTRACT

Objective:To explore the effects of foraging exercise (FE) on depressive-like behaviors and expression of transforming growth factor-β1 (TGF-β1) in hippocampus of rats with ischemic stroke after chronic stress.Methods:The right middle cerebral artery occlusion (MCAO) model was used in 30 male adult clean grade SD rats by suture method.According to the body weight, rats were evenly divided into stroke group ( n=10) and chronic unpredictable mild stimulation (CUMS) group ( n=20). Rats of CUMS group received stress induction 1 week after operation and lasted for 3 weeks. Then, according to random number generator of SPSS 24.0 software, the depression rats were divided into post-stroke depression (PSD) group( n=10) and FE groups ( n=10). The FE group received free FE intervention for 4 weeks. Body weight, water maze test, novelty inhibition feeding test (NSFT) and sucrose preference test (SPT) were performed at the end of the 1st, 4th and 8th week, respectively. The expression of TGF-β1 in hippocampus was detected by Immunohistochemistry (IHC) and Western blot (WB), and the levels of TGF-β1 and TNF-α in serum were detected by ELISA. SPSS 24.0 software was used for statistical analysis. The behavioral data were compared by two factor repeated measurement analysis of variance. One way ANOVA was used for comparison among groups, and LSD test was used for further pairwise comparison. Results:(1) The interaction between group and time had statistical significance on body weight, latency and food intake of NSFT and sucrose preference index(SPI) ( F=2.936-12.098, all P<0.05). After 4 weeks, compared with the stroke group((343.80±19.34)g, (12.10±6.97)s, (0.75±0.09)%), the body weight((307.80±17.23)g, (305.30±24.39)g), and SPI((0.52±0.06)%, (0.53±0.07)%) of PSD group and FE group were lower and the NSFT latency((21.70±7.02)s, (22.40±0.84)s) was longer (all P<0.05). After 8 weeks, SPI in FE group was higher than that in PSD group ( P=0.045). There were significant differences in body weight of three groups, NSFT latency and SPI of PSD group and FE group, and food intake of stroke and FE group ( F=8.478-196.548, all P<0.05). There was no interaction between group and time in the water maze test. Main effect of time ( P=0.034) and main effect of group ( P<0.01) had statistical significance on escape latency. The escape latency after 4 weeks was longer than that after 1 week ( P=0.003). The latency of PSD group was longer than that of stroke group ( P=0.005), and latency of FE group was shorter than that of the PSD group ( P<0.01). The main effect of group had statistical significance in the number of crossing quadrant ( P<0.01). The number of crossing quadrant of FE group was less than that of PSD group ( P<0.01). (2) Immunohistoche mistry staining showed that compared with the stroke group, the expression of TGF-β1 was down-regulated in 3 areas of hippocampus of PSD group (CA1, CA3 and DG) ( t=5.449-9.353, all P<0.01). Compared with stroke group, the expression of TGF-β1 of CA1 ( t=7.433, P<0.01) in FE group was down-regulated, but was up-regulated in CA3 ( t=3.342, P<0.05) of FE group. Compared with the PSD group, the expression of TGF-β1 was up-regulated in CA3 and DG of FE group ( t=7.811, 8.790, both P<0.01). (3) Western blot results: Compared with stroke group, the expression of TGF-β1 in hippocampus of PSD group was down-regulated ( t=3.255, P<0.01). Compared with the PSD group, the expression of TGF-β1 in hippocampus of FE group was up-regulated ( t=2.906, P<0.05). (4) ELISA detection showed that compared with the stroke group, the levels of TGF-β1 decreased ( t=2.224, P<0.05), but TNF-α increased ( t=6.127, P<0.01) in PSD group.Compared with the PSD group, the expression of TGF-β1 in FE group increased significantly ( t=4.417, P<0.01). Conclusion:Foraging exercise can improve the depressive behavior symptoms of ischemic stroke rats after chronic stress, and its mechanism may be related to the increasing expression of TGF-β1, which can alleviate the inflammatory reaction in hippocampus.

10.
Article in Chinese | WPRIM | ID: wpr-930158

ABSTRACT

Objective:To observe the effect of Hippocampus kelloggi on GRP-78/PERK/ATF-4 signal pathway and explore its mechanism on improving spinal cord injury. Methods:A total of 36 SD rats were randomly divided into sham operation group, model group and hippocampus group with 12 rats in each group. Only laminectomy was performed in the sham operation group. The spinal cord injury model was prepared in the model group and hippocampus group. Rats in the hippocampus group were given 10 ml/kg Hippocampus kelloggi extract by gavage for 14 days. Basso Beattie Bresnahan (BBB) score was used to evaluate the motor function of the limbs. The neuron morphology was observed by Nissl staining. The expression of GRP-78, p-PERK and ATF-4 proteins were detected by Western blot, the expression of GRP-78 and ATF-4 mRNAs was detected by qPCR, Caspase-3 and Caspase-12 were detected by ELISA, and the apoptosis was detected by TUNEL. Results:Compared with the model group, the BBB score of hippocampal group increased on the 7th, 9th, 11th and 14th day after operation ( P<0.05). For hippocampus group, the relative expression of GRP-78 (0.49 ± 0.06 vs. 0.74 ± 0.03), p-PERK (0.63 ± 0.04 vs. 0.81 ± 0.06) and ATF-4 (0.51 ± 0.06 vs. 0.69 ± 0.05) protein were significantly decreased ( P<0.05), GRP-78 mRNA (0.54 ± 0.05 vs. 0.63 ± 0.06) and ATF-4 mRNA (0.61 ± 0.06 vs. 0.78 ± 0.04) were significantly decreased ( P<0.05), the content of Caspase-3 and caspase-12 were significantly decreased ( P<0.05), and the apoptosis rate of hippocampal group was significantly decreased ( P<0.05). Conclusion:Hippocampus kelloggi can regulate the stress response of the endoplasmic reticulum after spinal cord injury by inhibiting GRP-78/PERK/ATF-4 signaling pathway to promote the repair of neurons.

11.
Article in Chinese | WPRIM | ID: wpr-940624

ABSTRACT

ObjectiveTo explore the mechanism of Naozhenning on learning and memory ability and neuron damage in hippocampal CA1 region of post-concussion syndrome model rats based on mitochondrial function. MethodMultiple cerebral concussion (MCC) was induced in SPF Wistar rats with the free-fall impact method. Then the model rats were randomly classified into model group (equivalent volume of distilled water), piracetam (0.43 g·kg-1, ig) group, and low-, medium-, and high-dose NZN (5.4, 10.8, 21.6 g·kg-1, respectively, ig) groups, with 10 rats in each group, and another 10 normal rats were included in the normal control group (equivalent volume of distilled water). The administration lasted 14 days and then relevant indexes were detected. Morris water maze test was used to observe the changes of learning and memory ability in each group, such as escape latency, residence time in primary quadrant, and times of crossing platform. The pathological changes of hippocampal CA1 region were observed based on hematoxylin-eosin (HE) staining and Nissl staining. The ultrastructure of mitochondria was observed under the transmission electron microscope (TME) and the activity of mitochondrial respiratory chain complex Ⅰ was detected by colorimetry. The content of adenosine triphosphate (ATP) was determined by fluorescence probe and mitochondrial membrane potential (MMP) by fluorescein enzyme-linked fluorescence immunoassay. ResultCompared with the normal control group, the model group showed long escape latency, short residence time in target quadrant, few times of crossing the platform, significant decrease in counts of neurons and Nissl bodies in hippocampal CA1 region, damage of neuronal morphology and mitochondrial structure, and significant reduction of MMP and the content of mitochondrial ATP and respiratory chain complex I (P<0.05, P<0.01). The NZN groups demonstrated short escape latency, long residence time in target quadrant, increased times of crossing the platform, small number of neurons and Nissl bodies in hippocampal CA1 region, alleviated damage of neuronal morphology and mitochondrial structure, and increase in MMP and the content of mitochondrial ATP and respiratory chain complex I (P<0.05, P<0.01). ConclusionNZN can improve the learning and memory ability of MCC rats by improving mitochondrial structure and function and alleviating hippocampal neuron injury.

12.
Article in English | WPRIM | ID: wpr-939588

ABSTRACT

Objective@#The hippocampus is thought to be a vulnerable target of microwave exposure. The aim of the present study was to investigate whether 20-hydroxyecdysone (20E) acted as a fate regulator of adult rat hippocampal neural stem cells (NSCs). Furthermore, we investigated if 20E attenuated high power microwave (HMP) radiation-induced learning and memory deficits.@*Methods@#Sixty male Sprague-Dawley rats were randomly divided into three groups: normal controls, radiation treated, and radiation+20E treated. Rats in the radiation and radiation+20E treatment groups were exposed to HPM radiation from a microwave emission system. The learning and memory abilities of the rats were assessed using the Morris water maze test. Primary adult rat hippocampal NSCs were isolated in vitro and cultured to evaluate their proliferation and differentiation. In addition, hematoxylin & eosin staining, western blotting, and immunofluorescence were used to detect changes in the rat brain and the proliferation and differentiation of the adult rat hippocampal NSCs after HPM radiation exposure.@*Results@#The results showed that 20E induced neuronal differentiation of adult hippocampal NSCs from HPM radiation-exposed rats via the Wnt3a/β-catenin signaling pathway in vitro. Furthermore, 20E facilitated neurogenesis in the subgranular zone of the rat brain following HPM radiation exposure. Administration of 20E attenuated learning and memory deficits in HPM radiation-exposed rats and frizzled-related protein (FRZB) reduced the 20E-induced nuclear translocation of β-catenin, while FRZB treatment also reversed 20E-induced neuronal differentiation of NSCs in vitro.@*Conclusion@#These results suggested that 20E was a fate regulator of adult rat hippocampal NSCs, where it played a role in attenuating HPM radiation-induced learning and memory deficits.


Subject(s)
Animals , Cell Proliferation , Ecdysterone/pharmacology , Hippocampus/metabolism , Male , Memory Disorders , Microwaves , Neural Stem Cells/physiology , Rats , Rats, Sprague-Dawley , beta Catenin/metabolism
13.
Article in Chinese | WPRIM | ID: wpr-927953

ABSTRACT

The effects of Jingui Shenqi Pills(Jingui) and Liuwei Dihuang Pills(Liuwei) which respectively tonify kidney Yang and kidney Yin on brain function have attracted great attention, while the differences of protein expression regulated by Jingui and Liuwei remain to be studied. This study explored the difference of protein expression profiles in the hippocampi of mice orally administrated with the two drugs for 7 days. The protein expression was quantified using LC-MS/MS. The results showed that among the 5 860 proteins tested, 151, 282 and 75 proteins responded to Jingui alone, Liuwei alone, and both drugs, respectively. The ratio of up-regulated proteins to down-regulated proteins was 1.627 in Jingui group while only 0.56 in Liuwei group. The proteins up-regulated by Jingui were mainly involved in membrane transport, synaptic vesicle cycle, serotonergic synapse, dopaminergic synapse and so on, suggesting that Jingui may play a role in promoting the transport of neurotransmitter in the nervous system. The proteins down-regulated by Liuwei were mainly involved in membrane transport, synapse, ion transport(potassium and sodium transport), neurotransmitter transport, innate and acquired immune responses, complement activation, inflammatory response, etc. In particular, Liuwei showed obvious down-regulation effect on the members of solute carrier(SLC) superfamily, which suggested that Liuwei had potential inhibitory effect on membrane excitation and transport. Finally, consistent results were obtained in the normal mouse and the mouse model with corticosterone-induced depressive-like behavior. This study provides an experimental basis for understanding the effect of Jingui and Liuwei on brain function from protein network.


Subject(s)
Animals , Chromatography, Liquid , Drugs, Chinese Herbal/pharmacology , Hippocampus/metabolism , Mice , Proteome/metabolism , Proteomics , Tandem Mass Spectrometry
14.
Article in Chinese | WPRIM | ID: wpr-927418

ABSTRACT

OBJECTIVE@#To observe the effect of wheat-grain moxibustion on behavior, 5-hydroxytryptamine (5-HT) and cortisol in the serum, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus in rats with hypothyroidism complicated with depression, and to explore the possible mechanism of wheat-grain moxibustion on improving depression in rats with hypothyroidism.@*METHODS@#A total of 32 SPF SD rats were randomly divided into a blank group, a model group, a medication group and a wheat-grain moxibustion group, 8 rats in each group. Except for the blank group, the rats in the remaining groups were treated with intragastric administration of 0.1% propylthiouracil (PTU) suspension at 1 mL/100 g, once a day for 4 weeks to establish the rat model of hypothyroidism, and whether the rats were accompanied with depression-like behavior determined through behavioristics evaluation. The rats in the medication group were intervened with euthyrox at 0.9 mL/100 g, once a day, for 4 weeks; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Mingmen" (GV 4), "Shenshu" (BL 23) and "Pishu" (BL 20), 7 cones each acupoint, once a day, six times a week for 4 weeks. After the intervention, the depression status was observed by behavioristics test; the contents of thyroid stimulating hormone (TSH), total thyroxine (TT4), 5-HT and cortisol in the serum were detected by ELISA; the protein expressions of MR and GR in hippocampus were detected by Western blot; the expressions of MR mRNA and GR mRNA in the hippocampus were detected by real-time PCR.@*RESULTS@#Before the intervention, compared with the blank group, the scores of open field test (OFT) were decreased and the immobility time of tail suspension test (TST) was prolonged (P<0.05); the serum TSH contents were increased and TT4 contents were decreased (P<0.01) in the other three groups. After the intervention, compared with the model group, the vertical score of OFT was increased and the immobility time of forced swimming test (FST) was prolonged in the medication group (P<0.05), while the scores of three items of OFT were increased (P<0.05, P<0.01), and the immobility time of FST and TST was shortened in the wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the medication group, the immobility time of TST and FST in the wheat-grain moxibustion group was shorter (P<0.05, P<0.01). Compared with the blank group, in the model group, the contents of serum TSH and cortisol were increased (P<0.01, P<0.001), while the contents of serum TT4 and 5-HT were decreased (P<0.01, P<0.001). Compared with the model group, the contents of serum TT4 and 5-HT were increased, while the contents of serum TSH and cortisol were decreased in the medication group and wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the blank group, the protein and mRNA expression of MR, GR in the hippocampus in the model group was decreased (P<0.01, P<0.05, P<0.001); compared with the model group, the protein and mRNA expression of MR in the hippocampus in the medication group were increased (P<0.05), and the protein expression of MR, GR and mRNA expression of MR in the hippocampus in the wheat-grain moxibustion group were increased (P<0.05, P<0.01). Compared with the medication group, the expression of MR mRNA in the wheat-grain moxibustion group was increased (P<0.05).@*CONCLUSION@#Wheat-grain moxibustion could significantly improve thyroid function and depression in rats with hypothyroidism. Its mechanism may be related to up-regulating the protein and mRNA expression of MR and GR in the hippocampus, and then affecting the expression of serum cortisol and 5-HT.


Subject(s)
Acupuncture Points , Animals , Depression/therapy , Hippocampus/metabolism , Hydrocortisone/metabolism , Hypothyroidism/therapy , Moxibustion , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Glucocorticoid/metabolism , Receptors, Mineralocorticoid/metabolism , Serotonin , Thyrotropin/metabolism , Triticum/metabolism
15.
Acta Pharmaceutica Sinica ; (12): 1452-1458, 2022.
Article in Chinese | WPRIM | ID: wpr-924743

ABSTRACT

The purpose of this study was to investigate the effect of isorhyncophylline on hippocampal endogenous metabolites in spontaneously hypertensive rats (SHR) by 1H NMR metabolomics and molecular docking. Twelve SHR were randomly divided into a model group and a treatment group. Six Wistar-Kyoto rats were selected as a control group. The rats in the treatment group were administered isorhyncophylline (0.3 mg·kg-1) while the rats in the other two groups were treated with the same amount of sterilized saline solution. Animal experiment was authorized by the Ethics Committee of Shandong University of Traditional Chinese Medicine (No. SDUTCM20210721002). Hippocampal tissues were removed after administration for 8 weeks and assayed by 1H NMR based metabolomics technology combined with a pattern recognition method to find characteristic metabolites, and the metabolic targets were retrieved from the Kyoto Encyclopedia of Genes and Genomes database. Molecular docking technology was used to evaluate binding of isorhyncophylline to the core targets. The results of a principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA) showed a clear cluster of samples among three groups. There were seven differentially altered metabolites, and glucose metabolism and glutamate metabolism were the principal related pathways. Molecular docking indicated that isorhyncophylline had good binding properties with nine key candidate target proteins. According to the above research results, isorhyncophylline can influence energy metabolism and glutamate metabolism in the hippocampus.

16.
Article in Chinese | WPRIM | ID: wpr-924058

ABSTRACT

Objective To study the effect of traditional Chinese medicine, Syngnathus on learning and memory impairment induced by D-galactose in aging mice and its mechanism of action. Methods HPLC was used to determine the content of DHA, the active ingredient in anti-learning and memory impairment in Syngnathus. The aging mouse model was prepared by intraperitoneal injection of D-galactose (D-gal). Morris water maze test and Western blot were used to detect the ability of learning and memory, biochemical indicators and protein expression related to oxidative damage in the hippocampus, and to explore the protective effect and mechanism of Syngnathus on learning and memory impairment in aging mice. Results HPLC results showed that the DHA content in Syngnathus was 7.761 3 mg/g (calculated as crude drug), accounting for about 47% of the total composition. Morris water maze results showed that Syngnathus could reduce the escape latency of learning and memory-impaired aging mice and increase the target quadrant swimming time, the proportion of swimming distance and the number of times of crossing the platform, and improve the learning and memory impairment of mice. In addition, Syngnathus can activate the AKT/FOXO1/SOD2 signaling pathway in the hippocampus of aging mice with learning and memory impairment, promote the expression of oxidative stress pathway-related proteins, and improve the learning and memory impairment in aging mice by reducing the degree of oxidative damage in the hippocampus of aging mice. Conclusion This study found that Syngnathus is rich in DHA, which has the effect of improving learning and memory impairment induced by D-galactose in aging mice, and preliminarily clarified that its mechanism of action is related to anti-oxidation. Experimental evidence is provided.

17.
Braz. J. Pharm. Sci. (Online) ; 58: e18807, 2022. graf
Article in English | LILACS | ID: biblio-1364413

ABSTRACT

Abstract This study aimed to investigate possible changes in the spatial memory of rats and the expression or activity of EGR-1, c-Fos, PKA, and PKC after propofol anesthesia. Thirty-six Sprague-Dawley rats aged 20 months and 36 Sprague-Dawley rats aged three months were each randomly divided into three groups: the control group, the Morris Water Maze (MWM) group, and the propofol group. In the propofol groups of both young and aged rats, the rats were anesthetized by propofol for two or four hours and then performed the MWM test two days or two weeks after anesthesia to assess cognitive function. EGR-1, c-Fos, PKA, and PKC expressions in the rat hippocampus were determined via immunohistochemistry. For the older rats, the escape latency in the P4h/2d group was significantly prolonged (P < 0.05), and the learning curve was right-shifted in the P4h/2w group (P < 0.05). The expression levels of EGR-1, c-Fos, PKA, and PKC in the MWM groups were significantly higher than those in the control groups (P < 0.05). In the P4h/2d group of aged rats, the expression levels of both PKA and PKC were decreased compared with those of the MWM groups. The decreased expression of both protein kinases may be responsible for the observed impairment after propofol anesthesia


Subject(s)
Animals , Male , Female , Rats , Propofol/pharmacology , Rats, Sprague-Dawley/classification , Morris Water Maze Test , Anesthesia/adverse effects , Cognition/classification , Cognitive Dysfunction/pathology , Spatial Memory , Hippocampus
18.
Braz. j. biol ; 81(3): 537-543, July-Sept. 2021. graf
Article in English | LILACS | ID: biblio-1153387

ABSTRACT

Abstract Anabolic substances have been increasingly used by bodybuilders and athletes with the goal of improving performance and aesthetics. However, this practice has caused some concern to physicians and researchers because of unknowledge of consequences that the indiscriminate and illicit use of these substances can cause. Thus, this study analyzed the effects of two commercially available anabolic steroids (AS), Winstrol Depot® (Stanozolol) and Deposteron® (Testosterone Cypionate), in the neuronal density of limbic, motor and sensory regions on the cerebral cortex and in CA1, CA2, CA3 regions of the hippocampus. A total of 60 Swiss mice were used (30 males and 30 females), separated into three groups: control and two experimental groups, which received the AAS. From each brain, homotypic and semi-serial samples were taken in frontal sections from areas established for the study. The results showed that females treated with testosterone cypionate presented a reduction in all regions tested and the ones treated with Stanozolol showed a decrease in some hippocampal areas. Regarding male animals, stanozolol led to a decrease in neuron number in one hippocampal region. These data allow us to conclude that supra-physiological doses of steroids used in this study, can cause considerable damage to nervous tissue with ultrastructural and consequently behavioral impairment. These changes could interfere with the loss of physical yield and performance of athletes and non-athletes and may cause irreparable damage to individuals making irresponsible use of anabolic steroids.


Resumo As substancias anabólicas tem sido cada vez mais utilizadas por fisiculturistas e atletas com o objetivo de melhorar o desempenho e a estética. No entanto, essa prática tem causado algumas preocupações aos médicos e pesquisadores, devido ao desconhecimento das consequencias que o uso indiscriminado e ilícito dessas substâncias podem causar. Diante disso, este estudo analisou os efeitos de dois esteroides anabolizantes (EA) comercialmente disponíveis, Winstrol Depot® (Stanozolol) e Deposteron® (cipionato de testosterona), na densidade neuronal das regiões corticais límbica, motora e sensitive bem como das áreas CA1, CA2, CA3 do hipocampo. Foram utilizados 60 camundongos Swiss (30 machos e 30 fêmeas), separados em três grupos: controle e dois grupos experimentais, que receberam o EA. De cada cérebro, foram coletadas amostras homotípicas e semi-seriadas em cortes frontais das áreas estabelecidas para o estudo. Os resultados mostraram que as fêmeas tratadas com cipionato de testosterona apresentaram uma redução em todas as regiões analisadas já as fêmeas tratadas com Stanozolol mostraram uma diminuição em algumas áreas do hipocampo. Em relação aos animais machos, o stanozolol levou a uma diminuição na densidade neuronal em uma região do hipocampo. Estes dados nos permitem concluir que doses supra fisiológicas de esteroides utilizadas neste estudo podem causar danos consideráveis ao tecido nervoso com comprometimento ultraestrutural e consequentemente comportamental. Essas alterações podem interferir na perda de rendimento físico e no desempenho de atletas e não atletas e podem causar danos irreparáveis a indivíduos que fazem uso irresponsável destes EA.


Subject(s)
Animals , Male , Female , Rabbits , Anabolic Agents/adverse effects , Stanozolol/adverse effects , Testosterone Congeners , Hippocampus , Neurons
19.
Int. j. morphol ; 39(2)abr. 2021.
Article in English | LILACS-Express | LILACS | ID: biblio-1385375

ABSTRACT

SUMMARY: Diabetes mellitus can lead to structural disorders in the brain. One of the most common complications of diabetes, diabetic neuropathy is associated with central nervous system disorders. Aloe vera has anti-diabetic, antioxidant, and neuroprotective effects. This study was designed to evaluate the effects of Aloe vera gel on the hippocampus changes as well as the expression of nerve growth factor and receptors TrkA and P75 in the hippocampus of streptozotocin (STZ)-induced diabetic rats. 25 male Wistar rats were randomly divided into 5 groups including: control (normal saline), diabetic (normal saline), Aloe vera gel (400 mg/kg/day; gavage), diabetic + Aloe vera gel (400 mg/kg/day; gavage) and diabetic + insulin NPH (10 IU/kg/day; subcutaneous). Experimental diabetes was induced by streptozotocin injection (60 mg/kg; intraperitoneal). All groups treated for 8 weeks. At the end of treatment course, the rat brains were removed for measuring the expression of nerve growth factor, p75 and TrkA receptors were evaluated in the hippocampus. Diabetes induction after 8 weeks caused NGF and P75 expression levels in the diabetic group than other groups significantly increased (p<0.05). The TrkA receptor expression in the diabetic group compared with the control had a significant reduction (p<0.05). On the other hand in the diabetic group receiving Aloe vera gel expression of NGF and P75 expression levels compared to the diabetic group was significantly reduced (p<0.05) and the TrkA receptor expression compared with the diabetic group had a significant increase (p<0.05). The results showed that oral administration of Aloe vera gel in diabetic rats ameliorates diabetes-induced hyperglycemia. On the other hand, Aloe vera gel cause modulation of the expression of NGF neurotrophic factor via increased expression of TrkA receptor-specific and non-specific receptor down-regulation of P75 in the hippocampus of STZ-induced diabetic rats.


RESUMEN: La diabetes mellitus puede provocar trastornos estructurales en el cerebro. Es una de las complicaciones más comunes de la diabetes y la neuropatía diabética y está relacionada con trastornos del sistema nervioso central. El Aloe vera tiene efectos antidiabéticos, antioxidantes y neuroprotectores. Este estudio fue diseñado para evaluar los efectos del gel de Aloe vera en los cambios del hipocampo, así como la expresión del factor de crecimiento nervioso y los receptores TrkA y P75 en el hipocampo de ratas diabéticas inducidas por estreptozotocina (STZ). Se dividieron al azar 25 ratas Wistar macho en 5 grupos de: control (solución salina normal), diabéticos (solución salina normal), gel de Aloe vera (400 mg / kg / día; sonda), diabéticos + gel de Aloe vera (400 mg / kg / día; sonda) y diabéticos + insulina NPH (10 UI / kg / día; subcutánea). La diabetes experimental fue inducida por inyección de estreptozotocina (60 mg / kg; intraperitoneal). Todos los grupos fueron tratados durante 8 semanas. Al final del tratamiento, se extrajeron los cerebros de las ratas para medir la expresión del factor de crecimiento nervioso y se evaluaron los receptores p75 y TrkA en el hipocampo. La inducción de diabetes después de 8 semanas provocó que los niveles de expresión de NGF y P75 en el grupo de diabéticos aumentaran significativamente en comparación con otros grupos (p <0,05). La expresión del receptor TrkA en el grupo diabético comparado con el control tuvo una reducción significativa (p <0,05). Por otro lado, el grupo de ratas diabéticas que recibieron la expresión en gel de Aloe vera de NGF y los niveles de expresión de P75 en comparación con el grupo de ratas diabéticas se redujo significativamente (p <0,05) y la expresión del receptor de TrkA en comparación con el grupo de ratas diabéticas tuvo un aumento significativo (p <0,05). Los resultados mostraron que la administración oral de gel de Aloe vera en ratas diabéticas mejora la hiperglucemia inducida por la diabetes. Por otro lado, el gel de Aloe vera causa modulación de la expresión del factor neurotrófico NGF a través del aumento de la expresión de receptor TrkA específico y no específico y regulación negativa del receptor de P75 en el hipocampo de ratas diabéticas inducidas por STZ.

20.
BrJP ; 4(1): 2-8, Jan.-Mar. 2021. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1249136

ABSTRACT

ABSTRACT BACKGROUND AND OBJECTIVES: To pursue safer and more effective treatments for rheumatoid arthritis, the effect of dexamethasone treatment (DEX, 0.25mg/kg) combined with transcranial direct current stimulation (tDCS) in the behavior and neurochemical parameters of arthritic rats was evaluated. METHODS: Thirty-six Wistar rats were divided into four groups: control+DEX (CTRL+DEX), arthritis+DEX (RA+DEX), arthritis+DEX+sham-tDCS (RA+DEX+sham-tDCS) and arthritis+DEX+tDCS (RA+DEX+tDCS). The arthritic model (RA) was induced by complete Freund's adjuvant (CFA) paw administration. Paw edema and mechanical allodynia were assessed by plethysmometer and von Frey apparatus, respectively. Fourteen days after the CFA injection, rats received the treatment for eight days (DEX and/or tDCS). Behavioral parameters were measured with the Open-Field test. ELISA was used to evaluate hippocampal and spinal cord tumor necrosis factor (TNF-α) levels, cerebral cortex and brainstem BDNF levels. RESULTS: In pre-treatment measurements, arthritic rats presented an increase in joint swelling and mechanical allodynia when compared to the control group, confirming chronic pain establishment. A slight antinociceptive effect of dexamethasone combined with tDCS in the pain model was observed. The pain model significantly induced an increase in the grooming behavior and a reduction in the spinal cord and hippocampal TNF-α levels; these effects were reverted in the sham- and active-tDCS-treated rats. However, no effects of DEX or tDCS were observed in the BDNF levels in the cerebral cortex and brainstem. CONCLUSION: Despite the small effect observed, tDCS treatment cannot be discarded as a non-pharmacological adjuvant technique for inflammatory chronic pain treatment.


RESUMO JUSTIFICATIVA E OBJETIVOS: Para investigar métodos mais seguros e eficazes para o manejo da artrite reumatoide, avaliou-se o efeito do tratamento com dexametasona (DEX, 0,25mg/kg) combinado com estimulação transcraniana por corrente contínua (ETCC) sobre parâmetros comportamentais e bioquímicos de ratos submetidos a um modelo de artrite reumatoide. MÉTODOS: Trinta e seis ratos Wistar foram alocados em 4 grupos: controle+DEX (CTRL+DEX), artrite+DEX (AR+DEX), artrite+DEX+sham-ETCC (AR+DEX+sham-ETCC) e artrite+DEX+ETCC (AR+DEX+ETCC). O modelo de artrite foi induzido pela administração de complete Freund's adjuvant (CFA) na pata. Edema na pata e a alodínia mecânica foram avaliadas por pletismômetro e teste de von Frey, respectivamente. 14 dias após injeção de CFA, ratos foram tratados por 8 dias (DEX e/ou ETCC). Atividade locomotora foi avaliada pelo teste do campo aberto. TNF-alfa (hipocampo e medula espinal) e BDNF (córtex e tronco) foram mensurados por ELISA. RESULTADOS: Nas medições pré-tratamento, ratos com artrite exibiram aumento de o inchaço articular e alodínia mecânica comparados ao grupo controle, confirmando o estabelecimento de modelo de dor crônica. Também se observou discreto efeito antinociceptivo da dexametasona combinada com ETCC no modelo de artrite. O modelo de dor induziu um aumento no comportamento de grooming e reduziu os níveis de TNF-alfa no hipocampo; estes efeitos foram revertidos nos grupos sham- e ETCC ativo. Entretanto, não foram observados efeitos da DEX ou ETCC nos níveis de BDNF no córtex cerebral ou no tronco encefálico. CONCLUSÃO: Apesar dos discretos efeitos observados, não se pode descartar a ETCC como uma abordagem terapêutica não farmacológica para o manejo da dor crônica inflamatória na artrite reumatoide.

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