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1.
Braz. j. otorhinolaryngol. (Impr.) ; 88(5): 787-793, Sept.-Oct. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1403930

ABSTRACT

Abstract Introduction Olfactory epithelium biopsy has been useful for studying diverse otorhinolaryngological and neurological diseases, including the potential to better understand the pathophysiology behind COVID-19 olfactory manifestations. However, the safety and efficacy of the technique for obtaining human olfactory epithelium are still not fully established. Objective This study aimed to determine the safety and efficacy of harvesting olfactory epithelium cells, nerve bundles, and olfactory epithelium proper for morphological analysis from the superior nasal septum. Methods During nasal surgery, 22 individuals without olfactory complaints underwent olfactory epithelium biopsies from the superior nasal septum. The efficacy of obtaining olfactory epithelium, verification of intact olfactory epithelium and the presence of nerve bundles in biopsies were assessed using immunofluorescence. Safety for the olfactory function was tested psychophysically using both unilateral and bilateral tests before and 1 month after the operative procedure. Results Olfactory epithelium was found in 59.1% of the subjects. Of the samples, 50% were of the quality necessary for morphological characterization and 90.9% had nerve bundles. There was no difference in the psychophysical scores obtained in the bilateral olfactory test (University of Pennsylvania Smell Identification Test [UPSIT®]) between means before biopsy: 32.3 vs. postoperative: 32.5, p= 0.81. Also, no significant decrease occurred in unilateral testing (mean unilateral test scores 6 vs. 6.2, p= 0.46). None out of the 56 different odorant identification significantly diminished (p> 0.05). Conclusion The technique depicted for olfactory epithelium biopsy is highly effective in obtaining neuronal olfactory tissue, but it has moderate efficacy in achieving samples useful for morphological analysis. Olfactory sensitivity remained intact.


Resumo Introdução A biópsia do epitélio olfatório tem sido útil para estudar diversas doenças otorrinolaringológicas e neurológicas, incluindo seu potencial para melhor compreender a fisiopatologia por trás das manifestações olfatórias na COVID‐19. No entanto, a segurança e eficácia da técnica de obtenção de epitélio olfatório humano ainda não estão totalmente estabelecidas. Objetivos Este estudo teve como objetivo determinar a segurança e eficácia da coleta de células do epitélio olfatório, feixes nervosos e epitélio olfatório adequados para análise morfológica, no septo nasal superior. Método Durante a cirurgia nasal, 22 indivíduos sem queixas olfatórias foram submetidos a biópsias de epitélio olfatório do septo nasal superior. A eficácia da obtenção de epitélio olfatório, a verificação de epitélio olfatório íntegro e a presença de feixes nervosos nas biópsias foram avaliadas por imunofluorescência. A segurança da função olfatória foi testada psicofisicamente usando testes unilaterais e bilaterais antes e um mês após o procedimento cirúrgico. Resultados Epitélio olfatório foi encontrado em 59,1% dos sujeitos. Das amostras, 50% apresentaram a qualidade necessária para a caracterização morfológica e 90,9% continham feixes nervosos. Não houve diferença nos escores psicofísicos obtidos no teste olfatório bilateral (University of Pennsylvania Smell Identification Test [UPSIT®]) entre as médias antes da biópsia: 32,3 vs. pós‐operatório: 32,5, p = 0,81. Além disso, nenhuma diminuição significante ocorreu no teste unilateral (escore médio do teste unilateral 6 vs. 6,2, p = 0,46). Não houve redução significante na identificação de nenhum dos 56 odorantes diferentes (p > 0,05). Conclusão A técnica descrita para biópsia de epitélio olfatório é altamente eficaz na obtenção de tecido olfatório neuronal, mas tem eficácia moderada na obtenção de amostras adequadas para análise morfológica. A capacidade olfativa permaneceu intacta.

2.
Gac. méd. Méx ; 158(4): 190-197, jul.-ago. 2022. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1404839

ABSTRACT

Resumen Introducción: La diabetes mellitus (DM) inhibe la biosíntesis de serotonina cerebral mediante cambios en la actividad y expresión de triptófano-5-hidroxilasa (TPH). Objetivos: Determinar si los cambios en la expresión de TPH1 y TPH2 cerebral y en el número de neuronas serotoninérgicas causados por la DM retornan a la normalidad en ratas con diabetes tratadas con insulina. Métodos: Ratas con diabetes inducida con estreptozotocina se dividieron en dos grupos uno tratado con insulina y otro sin tratamiento. En el día 14, se obtuvieron tallos cerebrales para cuantificar niveles de L-triptófano, 5-hidroxitriptamina y la actividad de la TPH. La expresión de TPH1 y TPH2 fue mediante Western blot y el número de neuronas serotoninérgicas por inmunohistoquímica. Resultados: En las ratas con diabetes se confirmó disminución de los niveles de L-triptófano, 5-hidroxitriptamina y la actividad de la TPH, así como menor expresión de TPH1 y TPH2 y menor número de neuronas serotoninérgicas. Cuando las ratas diabéticas fueron tratadas con insulina, el L-triptófano regresó a la normalidad, no así la 5-hidroxitriptamina, la expresión de TPH ni el número de neuronas serotoninérgicas. Conclusiones: La DM inhibe crónicamente la síntesis de 5-hidroxitriptamina cerebral mediante modificaciones en la expresión de TPH1 y TPH2 y disminución de las neuronas serotoninérgicas, que persisten a pesar del tratamiento con insulina.


Abstract Introduction: Diabetes mellitus (DM) inhibits brain serotonin biosynthesis through changes in tryptophan-5-hydroxylase (TPH) activity and expression. Objectives: To determine whether DM-induced changes in brain TPH1 and TPH2 expression and in the number of serotonergic neurons return to normal in diabetic rats treated with insulin. Methods: Rats with streptozotocin-induced diabetes were divided in two groups: one treated with insulin and the other without treatment. On day 14, brain stems were obtained in order to quantify L-tryptophan and 5-hydroxytryptamine levels, as well as to determine TPH activity. The expressión of TPH1 and THP2 by Western blot, and the number of serotonergic neurons by immunohistochemistry. Results: In diabetic rats, a decrease in the levels of L-tryptophan, 5-hydroxytryptamine and TPH activity was confirmed, as well as lower TPH1 and TPH2 expression and lower numbers of serotonergic neurons. When diabetic rats were treated with insulin, L-tryptophan returned to normal, but not 5-hydroxytryptamine, TPH expression, or the number of serotonergic neurons. Conclusions: DM chronically inhibits the synthesis of brain 5-hydroxytryptamine through changes in TPH1 and TPH2 expression and a decrease in the number of serotonergic neurons, which persist despite insulin treatment.

3.
Article in Chinese | WPRIM | ID: wpr-936375

ABSTRACT

OBJECTIVE@#To explore whether the characteristic responses to sound stimulations of the auditory neurons in the striatum is regulated in different behavioral states.@*METHODS@#The auditory neurons in the striatum of awake C57BL/6J mice were selected for this study. We recorded the auditory response of the striatum to noises over a long period of time by building a synchronous in vivo electrophysiological and locomotion recording system and using glass microelectrode attachment recording. By analyzing the running speed of the mice, the behavioral states of the mice were divided into the quiet state and the active state, and the spontaneous activity and evoked responses of the auditory neurons in the striatum were analyzed in these two states.@*RESULTS@#Compared with those recorded in the quiet state, the spontaneous activity of the auditory neurons in the striatum of the mice increased significantly (37.06±12.02 vs 18.51±10.91, P < 0.001) while the auditory response of the neurons decreased significantly (noise intensity=60 dB, 3.45±2.99 vs 3.04±2.76, P < 0.001) in the active state.@*CONCLUSION@#Locomotion has a significant inhibitory effect on the auditory response of the striatum, which may importantly contribute to the decline of sound information recognition ability in the active state.


Subject(s)
Acoustic Stimulation , Animals , Auditory Cortex/physiology , Evoked Potentials, Auditory , Locomotion/physiology , Mice , Mice, Inbred C57BL , Neurons
4.
Article in Chinese | WPRIM | ID: wpr-936287

ABSTRACT

OBJECTIVE@#To clarify the functional effects of differential expression of ring finger and tryptophan-aspartic acid 2 (RFWD2) on dendritic development and formation of dendritic spines in cerebral cortex neurons of mice.@*METHODS@#Immunofluorescent staining was used to identify the location and global expression profile of RFWD2 in mouse brain and determine the co-localization of RFWD2 with the synaptic proteins in the cortical neurons. We also examined the effects of RFWD2 over-expression (RFWD2-Myc) and RFWD2 knockdown (RFWD2-shRNA) on dendritic development, dendritic spine formation and synaptic function in cultured cortical neurons.@*RESULTS@#RFWD2 is highly expressed in the cerebral cortex and hippocampus of mice, and its expression level was positively correlated with the development of cerebral cortex neurons and dendrites. RFWD2 expression was detected on the presynaptic membrane and postsynaptic membrane of the neurons, and its expression levels were positively correlated with the length, number of branches and complexity of the dendrites. In cultured cortical neurons, RFWD2 overexpression significantly lowered the expressions of the synaptic proteins synaptophysin (P < 0.01) and postsynapic density protein 95 (P < 0.01), while RFWD2 knockdown significantly increased their expressions (both P < 0.05). Compared with the control and RFWD2-overexpressing cells, the neurons with RFWD2 knockdown showed significantly reduced number of dendritic spines (both P < 0.05).@*CONCLUSION@#RFWD2 can regulate the expression of the synaptic proteins, the development of the dendrites, the formation of the dendritic spines and synaptic function in mouse cerebral cortex neurons through ubiquitination of Pea3 family members and c-Jun, which may serve as potential treatment targets for neurological diseases.


Subject(s)
Animals , Aspartic Acid/metabolism , Cerebral Cortex , Dendritic Spines/metabolism , Mice , Neurons/metabolism , Synapses , Tryptophan/metabolism
5.
Neuroscience Bulletin ; (6): 263-274, 2022.
Article in English | WPRIM | ID: wpr-929087

ABSTRACT

Protein O-GlcNAcylation is a post-translational modification that links environmental stimuli with changes in intracellular signal pathways, and its disturbance has been found in neurodegenerative diseases and metabolic disorders. However, its role in the mesolimbic dopamine (DA) system, especially in the ventral tegmental area (VTA), needs to be elucidated. Here, we found that injection of Thiamet G, an O-GlcNAcase (OGA) inhibitor, in the VTA and nucleus accumbens (NAc) of mice, facilitated neuronal O-GlcNAcylation and decreased the operant response to sucrose as well as the latency to fall in rotarod test. Mice with DAergic neuron-specific knockout of O-GlcNAc transferase (OGT) displayed severe metabolic abnormalities and died within 4-8 weeks after birth. Furthermore, mice specifically overexpressing OGT in DAergic neurons in the VTA had learning defects in the operant response to sucrose, and impaired motor learning in the rotarod test. Instead, overexpression of OGT in GABAergic neurons in the VTA had no effect on these behaviors. These results suggest that protein O-GlcNAcylation of DAergic neurons in the VTA plays an important role in regulating the response to natural reward and motor learning in mice.


Subject(s)
Animals , Dopaminergic Neurons/physiology , GABAergic Neurons/physiology , Mice , Nucleus Accumbens/metabolism , Reward , Ventral Tegmental Area/metabolism
6.
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
7.
Chinese Journal of Neurology ; (12): 358-362, 2022.
Article in Chinese | WPRIM | ID: wpr-933802

ABSTRACT

Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare, low-grade neoplasm, which is newly categorized into the neuronal and mixed neuro-glial tumor in 2016. The most characteristic imaging findings are diffuse leptomeningeal thickening and enhancement with multiple minor cysts. This article described a case with DLGNT mimicking meningitis, whose cystic lesions were not obvious, with swollen multiple lobes cortex, gyri form cortical calcification and enhanced meninges. Meningeal irritation sign repeated attacks and the clinical symptoms gradually improved after steroid pulse therapy. The biopsy and immunohistochemistry staining were diagnosed as DLGNT. The imaging features and clinical data of this case were analyzed to improve the understanding of the disease in clinical practice.

8.
Article in Chinese | WPRIM | ID: wpr-933324

ABSTRACT

Objective:To evaluate the effect of propofol on neuronal activity in medial prefrontal cortex (mPFC) during social behavior in sleep-deprived rats.Methods:Sixty SPF healthy male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group Con), chronic sleep deprivation plus natural sleep group (group CSD+ NS), and chronic sleep deprivation plus propofol group (CSD+ Pro). Sleep deprivation model was developed by the modified multiple platform method, and the rats were placed in the sleep-deprivation tank for 20 h a day (14: 00-10: 00) and allowed to sleep naturally for 4 h (10: 00-14: 00) a day for 28 consecutive days.Propofol 40 mg/kg was intraperitoneally injected after sleep deprivation for 28 consecutive days in group CSD+ Pro, while the equal volume of 10% fat emulsion was given instead in group C and group CSD+ NS.Electroencephalographic recordings in cerebral cortical regions were performed on the days 1st, 14th and 28th after sleep deprivation.The apoptotic neurons in mPFC were detected using TUNEL method after the end of sleep deprivation, and the apoptosis index was calculated.A three chamber sociability test was used to detect the social behavior of rats, and local field potential signals in mPFC were collected. Results:Compared with group Con, the percentage of rapid eye movement sleep was significantly increased, the sniffing time preference coefficients in the 2 stages were reduced, the percentage of the β waves and θ waves-band power in mPFC during the social sniffing process was decreased, and the apoptosis index of neurons in mPFC was increased in group CSD+ NS ( P<0.05). Compared with group CSD+ NS, the percentage of rapid eye movement sleep was significantly increased, the sniffing time preference coefficient in the 2 stages was increased, and the percentage of β waves and θ waves-band power in mPFC during the social sniffing process was increased, and the apoptosis index of neurons in mPFC was decreased in group CSD+ Pro ( P<0.05). Conclusions:Propofol inhibits the apoptosis in neurons in mPFC and increases β and θ waves in the mPFC during social interaction after sleep deprivation in sleep-deprived rats, which is helpful in improving sleep deprivation-induced social disorder.

9.
Article in Chinese | WPRIM | ID: wpr-933296

ABSTRACT

Objective:To evaluate the role of N-methyl-D-aspartate receptors (NMDA receptors) in sevoflurane anesthesia-caused necroptosis in hippocampal neurons of aged mice.Methods:Ninety clean-grade healthy male C57BL/6 mice, aged 18 months, weighing 27-30 g, were divided into 3 groups ( n=30 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group S) and sevoflurane anesthesia plus NMDA receptor antagonist memantine hydrochloride group (group S+ M). Mice inhaled 3% sevoflurane for 2 h for 3 consecutive days in S group and S+ M group, and memantine hydrochloride 20 mg/kg was intraperitoneally injected at 1 h before each inhalation of sevoflurane in S+ M group.Mice only inhaled pure oxygen for 2 h in group C. Ten mice of each group were selected on 1 day before anesthesia and 3 and 7 days after anesthesia to perform Morris water maze test.The mice were sacrificed immediately after Morris water maze test, and hippocampus was removed for microscopic examination of pathological changes (with a light microscope) and for determination of the necroptosis rate of neurons and cytoplasmic free calcium concentration([Ca 2+ ] i)(by flow cytometry), and expression of NMDA receptor subtypes GluN2A, GluN2B and receptor-interacting protein kinase 1 (RIP1) (by Western blot). Results:Compared with group C, the escape latency was significantly prolonged, and the frequency of crossing the original platform was decreased, and the [Ca 2+ ] i and neuronal necroptosis rate in the hippocampus were increased at each time point after anesthesia, and the expression of GluN2A, GluN2B and RIP1 was up-regulated( P<0.05), and the pathologic changes were accentuated in S group and S+ M group.Compared with group S, the escape latency was significantly shortened, and the frequency of crossing the original platform was increased, and the [Ca 2+ ] i and neuronal necroptosis rate in the hippocampus were decreased at each time point after anesthesia, and the expression of GluN2A, GluN2B and RIP1 was down-regulated ( P<0.05), and the pathologic changes were attenuated in group S+ M. Conclusions:NMDA receptors are involved in the process of cognitive dysfunction induced by sevoflurane anesthesia in aged mice, and the mechanism may be related to the promotion of necrptosis in hippocampal neurons.

10.
Chinese Journal of Trauma ; (12): 260-267, 2022.
Article in Chinese | WPRIM | ID: wpr-932236

ABSTRACT

Objective:To investigate effect of miR-20b on the motor dysfunction after traumatic brain injury (TBI) in mice and the underlying mechanism.Methods:Sixty C57BL/6J mice were divided into sham group, TBI group and TBI+miR-20b Agomir (Agomir-20b) group according to the random number table, with 20 mice per group. A model of severe TBI was induced by controlled cortical impact. After injury, the mice in TBI group were subjected to tail-vein injection of 200 μl Agomir-negative control at dosage of 50 μmol/L and the mice in TBI+Agomir-20b group were subjected to tail-vein injection of 200 μl Agomir-20b at dosage of 50 μmol/L. At days 3 and 7 postinjury, the rate of neuronal apoptosis in the pericontusional region was detected by TUNEL assay, expression levels of apoptosis-related proteins in the pericontusional region were detected by Western blot analysis, including cleaved caspase-3, cleaved poly adenosine diphosphate-ribose polymerases (PARP), B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax), motor function was evaluated by beam walking test, and expression levels of cytokine mRNAs in the pericontusional region were detected by real-time quantitative PCR (RT-qPCR), including interleukin (IL)-1β, IL-6, IL-10, inducible nitric oxide synthase (iNOS), arginase (Arg) and macrophage mannose receptor 1 (CD206).Results:In TUNEL assay, the rate of neuronal apoptosis in sham group was significantly lower than that in TBI group and TBI+Agomir-20b group at days 3 and 7 postinjury (all P<0.01), and there was a significantly lower rate of neuronal apoptosis in TBI+Agomir-20b group as compared with TBI group (all P<0.01). In Western blot analysis, significantly increased levels of cleaved caspase-3, cleaved PARP and Bax proteins and lowered level of Bcl-2 protein were observed in TBI group at days 3 and 7 postinjury as compared with sham group (all P<0.01); similar levels of cleaved caspase-3, cleaved PARP and Bax proteins were found in TBI+Agomir-20b group at days 3 and 7 postinjury as compared with sham group (all P>0.05), and level of Bcl-2 protein in TBI+Agomir-20b group also showed no obvious variation at day 7 postinjury as compared with sham group ( P>0.05) in regardless of a significant reduction at day 3 postinjury ( P<0.01). Significantly increased levels of cleaved caspase-3, cleaved PARP and Bax proteins as well as a significantly reduced level of Bcl-2 protein were found in TBI group at days 3 and 7 postinjury as compared with TBI+Agomir-20b group (all P<0.05 or 0.01). In beam walking test, the latency and foot slip rate in TBI group were significantly higher than those in sham group and TBI+Agomir-20b group at days 3 and 7 postinjury (all P<0.01). In RT-qPCR analysis, levels of IL-1β, IL-6 and iNOS mRNA in TBI group were significantly higher than those in TBI+Agomir-20b group at days 3 and 7 postinjury (all P<0.01), but the two groups were similar in levels of IL-10, Arg and CD206 mRNA (all P>0.05). In comparison with sham group, levels of IL-1β, IL-6, iNOS and IL-10 mRNA in TBI+Agomir-20b group had no obvious change at days 3 and 7 postinjury (all P>0.05); level of Arg mRNA in TBI+Agomir-20b group was significantly increased at days 3 and 7 postinjury (all P<0.01); level of CD206 mRNA in TBI+Agomir-20b group did not change significantly at day 3 postinjury ( P>0.05), but was significantly increased at day 7 postinjury ( P<0.01). Conclusions:miR-20b can obviously inhibit neuronal apoptosis to improve motor function after TBI in mice, for which the underlying mechanism is related to Agomir-20b inhibiting the transformation of microglia to pro-inflammatory M1 type after TBI.

11.
Article in Chinese | WPRIM | ID: wpr-931682

ABSTRACT

Objective:To investigate the efficacy of Xiaoshuan Changrong Capsules combined with donepezil hydrochloride in the treatment of patients with vascular dementia and their effects on serum cytokines and oxidative stress. Methods:A total of 102 patients with vascular dementia who received treatment in Hangzhou Seventh People's Hospital, China between January 2019 and January 2021 were included in this study. They were randomly divided into control and observation groups, with 51 patients per group. The control group was treated by oral donepezil hydrochloride. The observation group was given oral Xiaoshuan Changrong Capsules combined with oral donepezil hydrochloride. All patients were treated for 12 weeks. Efficacy was compared between the two groups. The Clinical Dementia Rating score, the Mini-Mental State Examination score, and serum levels of interleukin 6, insulin-like growth factor-1, tumor necrosis factor-α, superoxide dismutase and malondialdehyde were compared between before and after treatment. Results:Total response rate in the observation group was significantly higher than that in the control group [90.20% (46/51) vs. 70.59% (36/51), χ 2 = 6.22, P < 0.05]. At 12 weeks after treatment, the Clinical Dementia Rating score in the observation group was significantly lower than that in the control group [(1.34 ± 0.27) points vs. (1.89 ± 0.31) points, t = 9.55, P < 0.05]. At 12 weeks after treatment, the Mini-Mental State Examination score in the observation group was significantly higher than that in the control group [(25.45 ± 1.98) points vs. (22.32 ± 2.10) points, t = 7.74, P < 0.05]. At 12 weeks after treatment, interleukin-6, insulin-like growth factor-1, and tumor necrosis factor-α levels in the observation group were (31.28 ± 7.35) ng/L, (0.34 ± 0.08) ng/L and (9.46 ± 2.27) ng/L, respectively, which were significantly lower than those in the control group [(46.43 ± 6.28) ng/L, (0.48 ± 0.07) ng/L, (20.98 ± 3.56) ng/L, t = 11.19, 9.40, 19.48, all P < 0.05]. At 12 weeks after treatment, superoxide dismutase in the observation group was significantly higher than that in the control group [(98.91 ± 7.25) U/L vs. (86.59 ± 5.63) U/L, t = 9.58, P < 0.05] . At 12 weeks after treatment, malondialdehyde in the observation group was significantly lower than that in the control group [(3.25 ± 0.50) mmol/L vs. (4.81 ± 0.35) mmol/L, t = 18.25, P < 0.05]. Conclusion:Xiaoshuan Changrong Capsules combined with donepezil hydrochloride is highly effective on vascular dementia. It can reduce cellular inflammatory response and improve oxidative stress response. This study is of great innovation and science.

12.
Article in Chinese | WPRIM | ID: wpr-929898

ABSTRACT

Cerebral small vessel disease (CSVD) is a common cerebrovascular disease in clinical practice. Its onset is hidden and its clinical manifestations are diverse. Studies have shown that there are pleiotropic effects and recurrent activation phenomenon between the functional imbalance of neurovascular unit (NVU) and a series of pathophysiological processes, such as vascular endothelial dysfunction, blood-brain barrier permeability change and glial cell activation, which jointly promote the progress of CSVD under the action of inflammatory and immune factors. This article reviews the role of NVU in the occurrence and development of CSVD.

13.
Article in Chinese | WPRIM | ID: wpr-929794

ABSTRACT

As the main cell type in mammalian cortex, cortical projection neurons play an important role in brain functions, including motor control, sensation and cognition.Projection neurons in the cerebral cortex include excitatory projection neurons and inhibitory projection neurons, of which excitatory projection neurons are the main type.Cortical excitatory projection neurons have various subtypes, and most of them have their own unique developmental rules and molecular markers.Studying the origin and classification of projection neurons in the cerebral cortex is helpful to understand the mechanisms of diseases related to abnormal projection neurons.This paper reviews the origin, classification and function of cortical projection neurons.

14.
Acta Pharmaceutica Sinica B ; (6): 1305-1321, 2022.
Article in English | WPRIM | ID: wpr-929349

ABSTRACT

Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss. This study aimed to assess the potential effect of the DNA methyltransferase (DNMT) inhibitor RG108 on cisplatin-induced ototoxicity. Immunohistochemistry, apoptosis assay, and auditory brainstem response (ABR) were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells (HCs) and spiral ganglion neurons (SGNs). Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential (MMP) assessment. Reactive oxygen species (ROS) amounts were evaluated by Cellrox green and Mitosox-red probes. Mitochondrial respiratory function evaluation was performed by determining oxygen consumption rates (OCRs). The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs, and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS accumulation. Furthermore, RG108 upregulated BCL-2 and downregulated APAF1, BAX, and BAD in HEI-OC1 cells, and triggered the PI3K/AKT pathway. Decreased expression of low-density lipoprotein receptor-related protein 1 (LRP1) and high methylation of the LRP1 promoter were observed after cisplatin treatment. RG108 treatment can increase LRP1 expression and decrease LRP1 promoter methylation. In conclusion, RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.

15.
Article in English | WPRIM | ID: wpr-929241

ABSTRACT

Parkinson's disease (PD) is a multifactorial disorder of the nervous system where a progressive loss of dopaminergic neurons exist. However, the pathogenesis of PD remains undefined, which becomes the main limitation for the development of clinical PD treatment. Demethylenetetrahydroberberine (DMTHB) is a novel derivative of natural product berberine. This study was aimed to explore the neuroprotective effects and pharmacological mechanism of DMTHB on Parkinson's disease using C57BL/6 mice. A PD model of mice was induced by administration of MPTP (20 mg·kg-1) and probenecid (200 mg·kg-1) twice per week for five weeks. The mice were administered with DMTHB daily by gavage at the dose of 5 and 50 mg·kg-1 for one- week prophylactic treatment and five-week theraputic treatment. The therapeutic effects of DMTHB were evaluated by behavior tests (the open field, rotarod and pole tests), immunohistochemical staining of tyrosine hydroxylase (TH), Nissl staining and biochemical assays. The molecular mechanisms of DMTHB on the key biomarkers of PD pathological states were analyzed by Western blot (WB) and qRT-PCR. DMTHB treatment alleviated the behavioral disorder induced by MPTP-probenecid. Nissl staining and TH staining showed that the damage of dopaminergic neurons in the substantia nigra was remarkably suppressed by DMTHB treatment. Western blot results showed that the ratio of Bcl-2/Bax and TH increased, but the level of α-synuclein (α-syn) was remarkably reduced, which indicated that the apoptosis of dopaminergic neurons in mice was significantly reduced. The protein phosphorylation of p-PI3K, p-AKT and p-mTOR also increased about 2-fold, compared with the model group. Furthermore, qRT-PCR results demonstrated that the mRNA levels of pro-inflammatory cytokines, IL-1β and TNF-α, were reduced, but the level of anti-inflammatory cytokine IL-10 increased after DMTHB treatment. Finally, the cellular assay displayed that DMTHB was also a strong antioxidant to protect neuron cell line PC12 by scavenging ROS. In this study, we demonstrated DMTHB alleviates the behavioral disorder and protects dopaminergic neurons through multiple-target effects includubg anti-apoptotic, anti-inflammatory and antioxidant effects.


Subject(s)
Animals , Dopaminergic Neurons/pathology , Mice , Mice, Inbred C57BL , Parkinson Disease/pathology , Parkinsonian Disorders/chemically induced , Substantia Nigra
16.
Neuroscience Bulletin ; (6): 135-148, 2022.
Article in English | WPRIM | ID: wpr-922667

ABSTRACT

The family of voltage-gated potassium Kv2 channels consists of the Kv2.1 and Kv2.2 subtypes. Kv2.1 is constitutively highly phosphorylated in neurons and its function relies on its phosphorylation state. Whether the function of Kv2.2 is also dependent on its phosphorylation state remains unknown. Here, we investigated whether Kv2.2 channels can be phosphorylated by protein kinase C (PKC) and examined the effects of PKC-induced phosphorylation on their activity and function. Activation of PKC inhibited Kv2.2 currents and altered their steady-state activation in HEK293 cells. Point mutations and specific antibodies against phosphorylated S481 or S488 demonstrated the importance of these residues for the PKC-dependent modulation of Kv2.2. In layer II pyramidal neurons in cortical slices, activation of PKC similarly regulated native Kv2.2 channels and simultaneously reduced the frequency of action potentials. In conclusion, this study provides the first evidence to our knowledge that PKC-induced phosphorylation of the Kv2.2 channel controls the excitability of cortical pyramidal neurons.


Subject(s)
Action Potentials , HEK293 Cells , Humans , Protein Kinase C/metabolism , Pyramidal Cells/enzymology , Shab Potassium Channels/genetics
17.
Acta cir. bras ; 37(8): e370804, 2022. tab, graf
Article in English | LILACS-Express | LILACS, VETINDEX | ID: biblio-1402974

ABSTRACT

ABSTRACT Purpose: Various postoperative protocols have been proposed to improve outcomes and accelerate nerve regeneration. Recently, the use of physical exercise in a post-surgical neurorraphy procedure has shown good results when started early. We experimentally investigated the hypothesis that post-operative exercise speeds up results and improves clinical and morphologic parameters. Methods: Isogenic rats were randomly divided into four groups: 1 SHAM; 2 SHAM submitted to the exercise protocol (EP); 3 Grafting of the sciatic nerve; and 4 Grafting of the sciatic nerve associated with the EP. The EP was based on aerobic activities with a treadmill, with a progressive increase in time and intensity during 6 weeks. The results were evaluated by the sciatic functional index (SFI), morphometric and morphologic analysis of nerve distal to the lesion, and the number of spinal cord motor neurons, positive to the marker Fluoro-Gold (FG), captured retrogradely through neurorraphy. Results: Functional analysis (SFI) did not show a statistical difference between the group grafted with (-50.94) and without exercise (-65.79) after 90 days. The motoneurons count (Spinal cord histology) also showed no diference between these groups (834.5 × 833 respectively). Although functionally there is no difference between these groups, morphometric study showed a greater density (53.62) and larger fibers (7.762) in GRAFT group. When comparing both operated groups with both SHAM groups, all values were much lower. Conclusions: The experimental model that this aerobic treadmill exercises protocol did not modify nerve regeneration after sciatic nerve injury and repair with nerve graft.

18.
São Paulo; s.n; s.n; 2022. 111 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1396973

ABSTRACT

O objetivo desse trabalho foi identificar as consequências moleculares e funcionais da falta da proteína Ric8b no epitélio olfatório de camundongos. Para esse fim, comparamos o transcriptoma de epitélio olfatório de camundongos knock-out tecido específico para a proteína RIC8B (Ric8b cKO) com o dos seus irmãos tipo selvagem (WT). Identificamos muitos genes que apresentaram expressão reduzida no epitélio olfatório do camundongo Ric8b cKO, mas também vários genes que apresentaram a sua expressão aumentada. A maioria dos genes com expressão reduzida corresponde a genes normalmente expressos em neurônios olfatórios maduros, como por exemplo os genes de receptores olfatórios, o que é compatível com o fato já conhecido de que os camundongos Ric8b cKO apresentam um menor número desses neurônios. Inesperadamente, apesar de a maioria dos genes de receptores olfatórios ter a sua expressão diminuída no camundongo Ric8b cKO, observamos que um grupo destes genes de receptores teve a sua expressão aumentada. Os camundongos Ric8b cKO apresentaram também genes marcadores de outros tipos celulares que não neurônios canônicos com expressão aumentada no seu epitélio olfatório. Dentre eles, os mais significativamente alterados foram os genes marcadores de neurônios Trpc2+ tipo B (que expressam a guanilato ciclase solúvel Gucy1b2). Sabe-se que este tipo de neurônio é responsável pela sensibilidade a diferentes gases, e concordantemente, observamos que os camundongos Ric8b cKO apresentaram um aumento da sensibilidade a gás carbônico. Como o olfato apresenta um papel importante na regulação de ingestão alimentar, analisamos como os camundongos Ric8b cKO se comportam frente a diferentes dietas. Interessantemente, observamos que esses animais não apresentam preferência por alimento rico em gorduras quando comparado aos seus irmãos tipo selvagem. Nossos resultados sugerem, portanto, que a ausência da proteína RIC8B resulta na alteração de representatividade de neurônios canônicos e não canônicos no epitélio olfatório de camundongos, o que por sua vez leva a alterações funcionais e comportamentais


The objective of this work was to identify the molecular and functional consequences of the lack of the RIC8B protein in the main olfactory epithelium of mice. To this end, we compared the olfactory epithelium transcriptome of Ric8b tissue-specific knock-out mice (Ric8b cKO) with that of their wild-type littermates (WT). We identified many genes with differential expression, many of which were downregulated and also some which were upregulated in the olfactory epithelium of the Ric8b cKO mice. Most of the downregulated genes correspond to genes normally expressed in mature olfactory sensory neurons, such as olfactory receptor genes. This is compatible with the already known fact that the Ric8b cKO mice have less of this kind of neuron. Unexpectedly, even though most of the olfactory receptor genes were downregulated, we observed a subset of these genes that had their expression upregulated in the Ric8b cKO mice. The Ric8b cKO mice also showed upregulation for genes that are markers for cell types other than canonic neurons in their olfactory epithelium. Among these, the most significantly altered were the markers for neurons Trpc2+ type B (that express the soluble guanylate cyclase Gucy1b2). It is known that this kind of neuron is responsible for sensitivity to different gases. Accordingly, we observed that the Ric8b cKO mice presented a higher sensitivity to carbon dioxide. Since olfaction has an important role in food intake, we analyzed how the Ric8b cKO mice behaved with different diets. Interestingly, we observed that the Ric8b cKO mice lack preference for high fat diet when compared to their wild-type littermates. Our results indicate, therefore, that the lack of the RIC8B protein results in altered representativity of canonic and non-canonic neurons in the olfactory epithelium of mice, which then leads to altered function and behavior


Subject(s)
Animals , Male , Female , Mice , Olfactory Mucosa/abnormalities , Receptors, Odorant/agonists , Olfactory Receptor Neurons , Mice, Knockout , Feeding Behavior/classification , Neurons/chemistry , Absenteeism
19.
Rev. CEFAC ; 24(1): e10521, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1387199

ABSTRACT

ABSTRACT Purpose: to identify the usage profile of mirrors and electromyographic biofeedback to support myofunctional therapy by speech-language-hearing therapists who work with oral-motor function in Brazil. Methods: a quantitative cross-sectional study with an online (SurveyMonkey) questionnaire, which was structured with questions on the use of mirrors and/or electromyographic biofeedback. A descriptive analysis was made, and the Mann-Whitney U test and the chi-square test were applied (p < 0.05). Results: most professionals (23 [82.14%]) used mirrors, whereas only five (17.85%) used electromyographic biofeedback. The electromyographic biofeedback was used at some point with all age groups, to treat mastication and swallowing functions and facial mimics. Dysphagia and facial palsy were regularly or occasionally treated with it. The patients' perception was significantly associated with the use of either instrument. The electromyographic biofeedback group showed a consensus among patients, while approximately half of the mirror group (12 [52.17%]) were indifferent to its use. Conclusion: the profile showed young adult professionals, who used national equipment. The findings reinforce the need for research on complementary therapeutic procedures in the field of oral-motor functions, particularly, electromyographic biofeedback.


RESUMO Objetivo: identificar o perfil de uso do espelho e do Biofeedback Eletromiográfico como suporte à terapia miofuncional por Fonoaudiólogos atuantes na área de Motricidade Orofacial no Brasil. Métodos: estudo quantitativo e transversal, por meio da aplicação de questionário online (plataforma SurveyMonkey). O questionário foi estruturado com perguntas sobre o uso do espelho e/ou do Biofeedback Eletromiográfico. Foi realizada análise descritiva e aplicação dos Testes U de Mann-Whitney e Qui-quadrado (p<0,05). Resultados: a maioria dos profissionais, 23 (82,14%), utiliza o espelho, enquanto apenas cinco (17,85%) utilizam o biofeedback eletromiográfico. O Biofeedback Eletromiográfico é eventualmente utilizado em todas as faixas etárias, assim como para as funções de mastigação, deglutição e mímica facial. As patologias referidas com uso regular e eventual foram a disfagia e a paralisia facial. Houve associação significante na percepção dos pacientes em relação ao uso de algum dos instrumentos, porém no grupo do Biofeedback Eletromiográfico houve consenso entre os pacientes e, no grupo espelho, aproximadamente metade 12 (52,17%) achou indiferente. Conclusão: o perfil encontrado foi de profissionais adultos jovens, com uso de instrumentação nacional. Os achados reforçam a necessidade de pesquisas voltadas aos procedimentos terapêuticos complementares na área de Motricidade Orofacial, sobretudo Biofeedback Eletromiográfico.

20.
Arq. bras. neurocir ; 40(2): 146-151, 15/06/2021.
Article in English | LILACS | ID: biblio-1362220

ABSTRACT

Purpose Experimental models might help understand the pathophysiology of neurocysticercosis-associated hydrocephalus. The present study aimed to compare the extent of hydrocephalus and tissue damage in rats with subarachnoid inoculation of different concentrations of Taenia crassiceps cyst proteins. Methods Sixty young rats were divided into two groups: low- and high-concentration groups. The animals in the low concentration group received 0.02ml of 2.4mg/ml T. crassiceps cyst proteins while those in the high concentration group received 0.02 ml of 11.6mg/ml T. crassiceps cyst proteins. The animals underwent magnetic resonance imaging at 1, 3, and 6 months postinoculation to assess the ventricle volume. Morphological assessment was performed at the end of the observation period. Results Repeated measures of ventricle volumes at 1, 3, and 6 months showed progressive enlargement of the ventricles. At 1 and 3 months, we observed no differences in ventricle volumes between the 2 groups. However, at 6 months, the ventricles were larger in the high concentration group (median » 3.86mm3, range: 2.37­12.68) compared with the low concentration group (median » 2.00mm3, range: 0.37­11.57), p » 0.003. The morphological assessment revealed a few inflammatory features in both groups. However, the density of oligodendrocytes and neurons within the periventricular region was lower in the high concentration group (5.18 versus 9.72 for oligodendrocytes and 15.69 versus 21.00 for neurons; p < 0.001 for both). Conclusion Our results suggest that, in rats, a higher concentration of T. crassiceps cyst proteins in the subarachnoid space could induce ventricle enlargement and reduce the number of neurons within the periventricular area.


Subject(s)
Animals , Rats , Cerebral Ventricles/physiopathology , Neurocysticercosis/pathology , Hydrocephalus/parasitology , Antigens, Helminth , Subarachnoid Space/physiopathology , Taenia , Magnetic Resonance Imaging/methods , Rats, Wistar , Statistics, Nonparametric , Central Nervous System Parasitic Infections , Host-Parasite Interactions , Hydrocephalus/physiopathology
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