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Rev. bras. med. esporte ; 27(4): 405-409, Aug. 2021. graf
Article in English | LILACS | ID: biblio-1288596


ABSTRACT Objective: The paper uses artificial neural network images to explore the effects of aerobic exercise on the gamma rhythm of theta period in the awake hippocampal CA1 area of APP/PS1/tau mice and the low-frequency gamma rhythm of the sleep state hippocampal CA1 area SWR period. Methods: Clean grade 6-month-old APP/PS1/tau mice were randomly divided into quiet group (AS) and exercise group (AE), C57BL/6J control group mice were randomly divided into quiet group (CS) and exercise group (CE). The AE group and the CE group performed 12-week treadmill exercise, 5d/week, 60min/d, the first 10min exercise load was 12m/min, the last 50min was 15m/min treadmill slope was 0°. Eight-arm maze detection of behavioral changes in mice; multi-channel in vivo recording technology to record the electrical signals of the awake state and sleep state in the hippocampal CA1 area, MATLAB extracts the awake state theta period and sleep state SWR period, multi-window spectrum estimation method Perform time-frequency analysis and power spectral density analysis. Results: 12 weeks of aerobic exercise can significantly improve the working memory and reference memory of the AS group, increase the gamma energy in theta period of the awake hippocampus CA1 area and the low-frequency gamma energy in the sleep state CA1 area SWR period. Conclusions: Aerobic exercise can improve the neural network state of the AD model and increase the gamma energy in theta period of the hippocampus CA1 area, and the low-frequency gamma energy in the SWR period is one of the neural network mechanisms for its overall behavioral improvement. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Objetivo: o artigo usa imagens de redes neurais artificiais para explorar os efeitos do exercício aeróbio no ritmo gama do período teta na área CA1 do hipocampo desperto de camundongos APP/PS1/tau e o ritmo gama de baixa frequência da área CA1 do hipocampo do estado de sono Período SWR. Métodos: Camundongos APP/PS1/tau de grau limpo de 6 meses de idade foram divididos aleatoriamente em grupo quieto (AS) e grupo de exercício (AE), os camundongos do grupo controle C57BL/6J foram divididos aleatoriamente em grupo quieto (CS) e grupo de exercício (CE). O grupo AE e o grupo CE realizaram 12 semanas de exercício em esteira, 5d/semana, 60min/d, a primeira carga de exercício de 10min foi de 12m/min, a última de 50min foi de 15m/min e a inclinação da esteira foi de 0 °. Detecção de labirinto de oito braços de mudanças comportamentais em camundongos; tecnologia de gravação in vivo multicanal para registrar os sinais elétricos do estado de vigília e do estado de sono na área CA1 do hipocampo, MATLAB extrai o período de tempo teta do estado de vigília e o período de tempo SWR do estado de sono, método de estimativa de espectro de múltiplas janelas. e análise de densidade espectral de potência. Resultados: 12 semanas de exercícios aeróbicos podem melhorar significativamente a memória de trabalho e a memória de referência do grupo AS, aumentar a energia gama no período teta da área CA1 do hipocampo acordado e a energia gama de baixa frequência na área CA1 do estado de sono período SWR. Conclusões: O exercício aeróbico pode melhorar o estado da rede neural do modelo AD e aumentar a energia gama no período teta da área CA1 do hipocampo e a energia gama de baixa frequência no período SWR é um dos mecanismos da rede neural para seu comportamento geral. Nível de evidência II; Estudos terapêuticos- investigação dos resultados do tratamento.

RESUMEN Objetivo: El artículo utiliza imágenes de redes neuronales artificiales para explorar los efectos del ejercicio aeróbico en el ritmo gamma del período theta en el área CA1 del hipocampo despierto de ratones APP/PS1/tau y el ritmo gamma de baja frecuencia del área CA1 del hipocampo en estado de sueño. Período de ROE. Métodos: Se dividieron aleatoriamente ratones APP/PS1/tau de 6 meses de edad de grado limpio en grupo tranquilo (AS) y grupo de ejercicio (AE), los ratones del grupo de control C57BL/6J se dividieron aleatoriamente en grupo tranquilo (CS) y grupo de ejercicio (CE). El grupo de EA y el grupo de EC realizaron 12 semanas de ejercicio en cinta rodante, 5 días a la semana, 60 min/d, la primera carga de ejercicio de 10 min fue de 12 m/min, los últimos 50 min fueron de 15 m/min y la pendiente de la cinta fue de 0 °. Detección en laberinto de ocho brazos de cambios de comportamiento en ratones; tecnología de grabación in vivo multicanal para registrar las señales eléctricas del estado despierto y del estado de sueño en el área CA1 del hipocampo, MATLAB extrae el período de tiempo theta del estado despierto y el período de tiempo de SWR del estado de suspensión, método de estimación de espectro de múltiples ventanas Realizar análisis de tiempo-frecuencia y análisis de densidad espectral de potencia. Resultados: 12 semanas de ejercicio aeróbico pueden mejorar significativamente la memoria de trabajo y la memoria de referencia del grupo AS, aumentar la energía gamma en el período theta del área CA1 del hipocampo despierto y la energía gamma de baja frecuencia en el período SWR del área CA1 del estado de sueño. Conclusiones: El ejercicio aeróbico puede mejorar el estado de la red neuronal del modelo AD y aumentar la energía gamma en el período theta del área del hipocampo CA1 y la energía gamma de baja frecuencia en el período SWR es uno de los mecanismos de la red neuronal para su comportamiento general. Nivel de evidencia II; Estudios terapéuticos- investigación de los resultados del tratamiento.

Animals , Mice , Exercise/physiology , Neural Networks, Computer , Gamma Rhythm/physiology , Hippocampus/diagnostic imaging , Models, Animal
Article in Chinese | WPRIM | ID: wpr-879153


In this paper, the extraction rate of crude polysaccharides and the yield of polysaccharides from Hippocampus served as test indicators. The comprehensive evaluation indicators were assigned by the R language combined with the entropy weight method. The Box-Behnken design-response surface methodology(BBD-RSM) and the deep neural network(DNN) were employed to screen the optimal parameters for the polysaccharide extraction from Hippocampus. These two modeling methods were compared and verified experimentally for the process optimization. This study provides a reference for the industrialization of effective component extraction from Chinese medicinals and achieves the effective combination of modern technology and traditional Chinese medicine.

Dietary Carbohydrates , Hippocampus , Neural Networks, Computer , Polysaccharides , Temperature
Article in Chinese | WPRIM | ID: wpr-879023


To explore the effect of Baihe Dihuang Decoction on the synaptic plasticity of hippocampal neurons in rats with anxious depression. Fifty SD rats were randomly divided into normal group, model group, venlafaxine group(6.75 mg·kg~(-1)), high-dose Baihe Dihuang Decoction group(8.64 g·kg~(-1)) and low-dose Baihe Dihuang Decoction group(4.32 g·kg~(-1)). Chronic restraint stress(6 h) combined with corticosterone(ih, 30 mg·kg~(-1)) was used to establish an anxious depression model, and 7 days after modeling, the administration started and continued for 21 days. The anxiety and depression-like behaviors of the rats were evaluated. Golgi-Cox staining and electron microscopy were used to observe the morphology and ultrastructural changes of synaptic dendrites. Immunofluorescence was used to detect the expression of hippocampal synaptic plasticity protein synapsin-1 and postsynaptic density protein 95(PSD-95). Western blot method was used to detect the expression of functional protein synaptophysin(SYP) and synaptic Ras GTPase activating protein(SynGap). The results showed that the rats in the model group had obvious anxiety and depression-like behaviors, the hip-pocampal dendritic spine density and branch length were reduced, the number of synapses was cut, and the internal structure was da-maged. The average fluorescence intensity of synapsin-1 and PSD-95 was significantly reduced and the expression of SYP and SynGap also decreased. High-dose Baihe Dihuang Decoction could significantly improve the anxiety and depression-like behaviors of model rats, relieve synaptic damage, and increase the expression of synapsin-1, PSD-95, SYP, and SynGap proteins. Therefore, we believe that Baihe Dihuang Decoction can improve anxiety and depression behaviors by regulating the synaptic plasticity of hippocampal neurons.

Animals , Depression/drug therapy , Hippocampus , Neuronal Plasticity , Rats , Rats, Sprague-Dawley , Synapses
Acta Physiologica Sinica ; (6): 10-16, 2021.
Article in Chinese | WPRIM | ID: wpr-878230


The aim of the present study was to observe the activation of microglia in the prefrontal cortex of type 1 diabetes mellitus (T1DM) mice, and the expression of the marker genes of the disease-associated microglia (DAM) associated with neurodegenerative diseases. Sixty healthy adult male C57BL/6J mice were randomly divided into two groups, normal control (CON) group and T1DM group. Streptozocin (STZ) was injected intraperitoneally to induce T1DM mice. The spatial learning and memory function of mice was detected by Morris water maze at the 8th week after the successful model establishment. The number and activation of microglia in the prefrontal cortex of mice were detected by immunofluorescence staining and Western blot. Changes in the mRNA level of several DAM molecular markers were detected by RT-FQ-PCR. The results showed that, compared with CON mice, the fasting blood glucose of T1DM mice increased significantly, while the body weight of T1DM mice decreased remarkably (P < 0.05). The escape latency of water maze in T1DM mice was longer than that in CON mice (P < 0.05). Compared with CON group, the Iba1 protein expression and the number of microglia in prefrontal cortex of T1DM group increased significantly (P < 0.05). In addition, the mRNA levels of several DAM markers in prefrontal cortex of T1DM group were increased significantly (P < 0.05). These results suggest that the microglia are activated and transformed to DAM type in the prefrontal cortex of T1DM mice.

Animals , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 1 , Hippocampus , Male , Mice , Mice, Inbred C57BL , Microglia , Prefrontal Cortex
Acta Physiologica Sinica ; (6): 1-9, 2021.
Article in Chinese | WPRIM | ID: wpr-878229


Astrocytes are a heterogenous group of macroglia present in all regions of the brain and play critical roles in many aspects of brain development, function and disease. Previous studies suggest that the B-cell lymphoma-2 associated X protein (BAX)-dependent apoptosis plays essential roles in regulating neuronal number and achieving optimal excitation/inhibition ratio. The aim of the present paper was to study whether BAX regulates astrocyte distribution in a region-specific manner. Immunofluorescence staining of SOX9 was used to analyze and compare astrocyte density in primary somatosensory cortex, motor cortex, retrosplenial cortex and hippocampus in heterozygous and homozygous BAX knockout mice at age of six weeks when cortical development has finished and glia development has reached a relatively steady state. The results showed that astrocyte density varied significantly among different cortical subdivisions and between cortex and hippocampus. In contrast to the significant increase in GABAergic interneurons, the overall and region-specific astrocyte density remained unchanged in the cortex when BAX was absent. Interestingly, a significant reduction of astrocyte density was observed in the hippocampus of BAX knockout mice. These data suggest that BAX differentially regulates neurons and astrocytes in cortex as well as astrocytes in different brain regions during development. This study provided important information about the regional heterogeneity of astrocyte distribution and the potential contribution of BAX gene during development.

Animals , Astrocytes , Hippocampus , Interneurons , Mice , Neurons , bcl-2-Associated X Protein/genetics
Chinese Medical Journal ; (24): 326-333, 2021.
Article in English | WPRIM | ID: wpr-878020


BACKGROUND@#Anterior thalamic nuclei (ATN) deep brain stimulation (DBS) is an effective method of controlling epilepsy, especially temporal lobe epilepsy. Mossy fiber sprouting (MFS) plays an indispensable role in the pathogenesis and progression of epilepsy, but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown. This study aimed to investigate the effect of ATN-DBS on MFS, as well as potential signaling pathways by a kainic acid (KA)-induced epileptic model.@*METHODS@#Twenty-four rhesus monkeys were randomly assigned to control, epilepsy (EP), EP-sham-DBS, and EP-DBS groups. KA was injected to establish the chronic epileptic model. The left ATN was implanted with a DBS lead and stimulated for 8 weeks. Enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus. One-way analysis of variance, followed by the Tukey post hoc correction, was used to analyze the statistical significance of differences among multiple groups.@*RESULTS@#ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy. The number of ectopic granule cells was reduced in monkeys that received ATN stimulation (P < 0.0001). Levels of 3',5'-cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the hippocampus, together with Akt phosphorylation, were noticeably reduced in monkeys that received ATN stimulation (P = 0.0030 and P = 0.0001, respectively). ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions (all P < 0.0001).@*CONCLUSION@#ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells, which may be associated with the reduced MFS in chronic epilepsy. The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.

Adenosine Monophosphate , Anterior Thalamic Nuclei , Cyclic AMP-Dependent Protein Kinases , Deep Brain Stimulation , Epilepsy/therapy , Epilepsy, Temporal Lobe/therapy , Hippocampus , Humans , Mossy Fibers, Hippocampal , Signal Transduction
Article in Chinese | WPRIM | ID: wpr-877673


OBJECTIVE@#To observe the effect of electroacupuncture (EA) pretreatment on hippocampal oxidative stress in aged mice with postoperative cognitive dysfunction (POCD) and explore the relevant mechanism of EA pretreatment on the improvement of learning and memory in POCD aged mice.@*METHODS@#A total of 72 healthy male aged mice were randomized into a blank group, a model group, a medication group and an EA group, 18 mice in each one. In each group, 1-day, 3-day and 7-day subgroups were divided separately, 6 mice in each subgroup. In the EA group, "Baihui" (GV 20) and "Dazhui" (GV 14) were selected and stimulated with EA, using continuous wave (15 Hz, 1 mA), continuously for 30 min, once a day, for 5 days consecutively. In the medication group, 10% minocycline was injected intraperitoneally, 40 mg/kg, once a day, consecutively for 5 days. In the blank and the control group, intraperitoneal injection of 0.9% sodium chloride solution was given with equal dosage. Except the blank group, at the end of intervention, partial hepatectomy was conducted to establish POCD model in the rest groups. Morris water maze test was adopted to evaluate the learning and memory ability of the aged mice. ELISA was used to determine the contents of reactive oxygen species (ROS) and malondialdehyde (MDA) in the hippocampal tissue. Western blot method was applied to detect the protein expressions of superoxide dismutase 1 (SOD 1) and superoxide dismutase 2 (SOD 2) in the hippocampal tissue.@*RESULTS@#Compared with the blank group, the percentage of platform quadrant residence time was obviously reduced in the mice in the model group (@*CONCLUSION@#Electroacupuncture pretreatment at "Baihui" (GV 20) and "Dazhui" (GV 14) may increase the learning and memory ability of POCD aged mice, which is probably related to the decrease of oxidative stress and the strengthening of hippocampal antioxidant capacity.

Animals , Electroacupuncture , Hippocampus , Male , Memory , Mice , Oxidative Stress , Postoperative Cognitive Complications
Article in Chinese | WPRIM | ID: wpr-877608


OBJECTIVE@#To screen protein target in prevention and treatment with electroacupuncture (EA) for Alzheimer's disease (AD) and explore the potential mechanism of EA in prevention of AD.@*METHODS@#A total of 40 APP/PS1 transgenic young male mice, 1.5-month old, were randomized into an EA group and a model group, 20 mice in each one, and 20 C57BL/6J mice were chosen as the normal control group. After adaptive housing for 1 week, the mice in the EA group were stimulated with EA at "Baihui" (GV 20), "Fengfu" (GV 16) and "Shenshu" (BL 23), with intermittent wave, 10 Hz in frequency and 2 mA in electric intensity. EA was given once daily, 20 min each time. There was 1 day at interval after EA for 6 days each week. Totally, the intervention lasted for 16 weeks. On day 3 after the end of EA intervention, Morris water maze test was adopted to detect learning and memory abilities of mice in each group. After water maze test, the label-free method was used to measure the difference expressions in cerebral cortex and hippocampus. Using Western blot method, the expressions of guanylate binding protein beta 5 (GNB 5) and histone-H 3 in cerebral cortex and hippocampus were verified. Using immunohistochemical method, the expressions of amyloid beta protein (Aβ) in cerebral cortex and hippocampus were detected.@*RESULTS@#Compared with the normal control group, the escape latency (on day 2, 3 and 4) was prolonged, the frequency of crossing platform and the duration of platform stay were decreased in the mice of the model group (@*CONCLUSION@#The intervention with EA effectively prevents from the decline of learning and memory ability and the formation of Aβ senile plaques in cerebral cortex and hippocampus in young mouse models of AD after growing up. Besides, EA plays a regulatory function for protein expression differences induced by AD model.

Alzheimer Disease/therapy , Amyloid beta-Peptides/genetics , Animals , Disease Models, Animal , Electroacupuncture , Hippocampus , Male , Mice , Mice, Inbred C57BL , Proteomics
Article in English | WPRIM | ID: wpr-880327


BACKGROUND@#Prenatal stress can cause neurobiological and behavioral defects in offspring; environmental factors play a crucial role in regulating the development of brain and behavioral; this study was designed to test and verify whether an enriched environment can repair learning and memory impairment in offspring rats induced by prenatal stress and to explore its mechanism involving the expression of insulin-like growth factor-2 (IGF-2) and activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus of the offspring.@*METHODS@#Rats were selected to establish a chronic unpredictable mild stress (CUMS) model during pregnancy. Offspring were weaned on 21st day and housed under either standard or an enriched environment. The learning and memory ability were tested using Morris water maze and Y-maze. The expression of IGF-2 and Arc mRNA and protein were respectively measured by using RT-PCR and Western blotting.@*RESULTS@#There was an elevation in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy. Maternal stress's offspring exposed to an enriched environment could decrease their plasma corticosterone level and improve their weight. The offspring of maternal stress during pregnancy exhibited abnormalities in Morris water maze and Y-maze, which were improved in an enriched environment. The expression of IGF-2, Arc mRNA, and protein in offspring of maternal stress during pregnancy was boosted and some relationships existed between these parameters after being exposed enriched environment.@*CONCLUSIONS@#The learning and memory impairment in offspring of prenatal stress can be rectified by the enriched environment, the mechanism of which is related to the decreasing plasma corticosterone and increasing hippocampal IGF-2 and Arc of offspring rats following maternal chronic stress during pregnancy.

Animals , Cytoskeletal Proteins/metabolism , Female , Gene Expression Regulation , Hippocampus/metabolism , Insulin-Like Growth Factor II/metabolism , Learning , Learning Disabilities/psychology , Male , Memory Disorders/psychology , Nerve Tissue Proteins/metabolism , Pregnancy , Prenatal Exposure Delayed Effects/psychology , Random Allocation , Rats , Rats, Wistar , Social Environment , Stress, Psychological/genetics
Article in Chinese | WPRIM | ID: wpr-879859


OBJECTIVE@#To study the change and significance of hippocampal volume (HCV) in children with recurrent febrile seizures.@*METHODS@#A retrospective analysis was performed on the medical data and examination results of 34 children with recurrent febrile seizures who underwent two magnetic resonance plain scans of the head and the hippocampus from January 1, 2013 to September 30, 2019. According to the follow-up time, they were divided into the first follow-up group and the second follow-up group. According to prognosis, they were divided into a febrile seizure group, a non-febrile group and an epilepsy group. The change in HCV was analyzed and compared.@*RESULTS@#Total HCV was positively correlated with age (@*CONCLUSIONS@#HCV gradually increases with age in children with recurrent febrile seizures. Persistent seizures may damage the development of the hippocampus.

Child, Preschool , Hippocampus/diagnostic imaging , Humans , Infant , Magnetic Resonance Imaging , Retrospective Studies , Seizures , Seizures, Febrile
Braz. j. med. biol. res ; 54(5): e10717, 2021. tab, graf
Article in English | LILACS | ID: biblio-1180740


Scorpion venom is a Chinese medicine for epilepsy treatment, but the underlying mechanism is not clear. Scorpion venom heat-resistant peptide (SVHRP), a peptide isolated from the venom of Buthus martensii Karsch, has an anti-epileptic effect by reducing seizure behavior according to a modified Racine scale. The present study aimed to investigate the molecular mechanism of SVHRP on temporal lobe epilepsy. The hippocampus and hippocampal neurons from kainic acid-induced epileptic rats were treated with SVHRP at different doses and duration. Quantitative RT-PCR and immunoblotting were used to detect the expression level of brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY), cAMP-response element binding protein (CREB), stromal interaction molecule (STIM), and calcium release-activated calcium channel protein 1 (ORAI1). In the hippocampal tissues and primary hippocampal neuron cultures, SVHRP treatment resulted in increased mRNA and protein levels of BDNF and NPY under the epileptic condition. The upregulation of BDNF and NPY expression was positively correlated with the dose level and treatment duration of SVHRP in hippocampal tissues from kainic acid-induced epileptic rats. On the other hand, no significant changes in the levels of CREB, STIM, or ORAI1 were observed. SVHRP may exhibit an anti-epileptic effect by upregulating the expression of BDNF and NPY in the epileptic hippocampus.

Animals , Rats , Scorpion Venoms/toxicity , Epilepsy/chemically induced , Epilepsy/drug therapy , Peptides , Brain-Derived Neurotrophic Factor/metabolism , Hot Temperature , Hippocampus/metabolism , Kainic Acid/toxicity , Neurons
Braz. arch. biol. technol ; 64: e21180392, 2021. graf
Article in English | LILACS | ID: biblio-1249216


ABSTRACT The therapeutic effect of adipose tissue-derived stem cells (ADSCs) or RE on hippocampal neurogenesis and memory in Parkinsonian rats were investigated. Male rats were lesioned by bilateral intra-nigral injections of 6-OHDA and divided into six groups: 1. Lesion 2 and 3: RE and water groups were lesioned rats pretreated with RE or water, from 2weeks before neurotoxin injection and treated once a day for 8weeks post lesion. 4&5: Cell and α-MEM (α-minimal essential médium) received intravenous injection of BrdU-labeled ADSCs or medium, respectively from 10days post lesion until 8weeks later. 6: Sham was injected by saline instead of neurotoxin. Memory was assessed using Morris water Maze (MWM), one week before and at 1, 4 and 8weeks post 6-OHDA lesion. After the last probe, the animals were sacrificed and brain tissue obtained. Paraffin sections were stained using cresyl violet, anti-BrdU (Bromodeoxyuridine / 5-bromo-2'-deoxyuridine), anti-GFAP (Glial fibrillary acidic protein) and anti-TH antibodies. There was a significant difference of time spent in the target quadrant between groups during probe trial at 4 and 8 weeks' post- lesion. Cell and RE groups spent a significantly longer period in the target quadrant and had lower latency as compared with lesion. Treated groups have a significantly higher neuronal density in hippocampus compared to water, α-MEM and lesion groups. BrdU positive cells were presented in lesioned sites. The GFAP (Glial fibrillary acidic protein) positive cells were reduced in treated and sham groups compared to the water, α-MEM and lesion groups. Oral administration of RE (Rosemary extract) or ADSCs injection could improve memory deficit in the Parkinsonian rat by neuroprotection.

Parkinson Disease/physiopathology , Rosmarinus , Stem Cell Transplantation , Memory Disorders/therapy , Morris Water Maze Test , Hippocampus
Int. j. morphol ; 38(6): 1623-1630, Dec. 2020. graf
Article in English | LILACS | ID: biblio-1134489


SUMMARY: This study aims to investigate the Effects of Titanium dioxide nanoparticles (TiO2 NPs) on the stereological parameters in the dentate gyrus and the morphology of granular hippocampal neurons in adult mice. Adult male mice (n=20, weight average: 45 g) were randomly divided into four groups including: group receiving saline (controls), low-dose (LD) 2.5 mg/kg TiO TiO2 NPs, medium-dose (MD) 5 mg/kg TiO2 NPs and high-dose (HD) 10 mg/kg TiO2 NPs, daily using gavage for 35 days. To estimate the volume of the hippocampus, dentate gyrus, and sub-layers of dentate gyrus the Cavalieri principle was used. The physical dissector was used to determine the numerical density of dentate gyrus granular cells. For analyzing the morphology of dentate gyrus granular cells the qualitative Golgi staining was used. Our data showed that the total volume of the hippocampus, dentate gyrus and its sublayers including molecular, granular and polymorph in TiO2 treated mice decreased significantly compared to the control group. Moreover, the total number and numerical density of dentate gyrus granular sub layer cells showed a significant reduction in all three experimental groups compared to the control group. The granular cells of the dentate gyrus had shorter dendritic length and decreased dendritic branches in the TiO2-treated in comparison with the control mice. These data can justify the disorders related to memory, learning and hippocampus neurons damages due to using of TiO2 NPs.

RESUMEN: En este estudio se analizaron los efectos de las nanopartículas de dióxido de titanio (TiO2 NP) sobre los parámetros estereológicos en el giro dentado y la morfología de las neuronas granulares del hipocampo en ratones adultos. Se dividieron aleatoriamente ratones machos adultos (n = 20, promedio de peso: 45 g) en cuatro grupos: grupo que recibió solución salina (controles), dosis baja (LD) 2,5 mg/kg NP de TiO2, dosis media (MD) 5 mg/kg de NP de TiO2 y dosis altas (HD) de 10 mg/kg de NP de TiO2, por vía utilizando sonda durante 35 días. Para estimar el volumen del hipocampo, el giro dentado y las subcapas del giro dentado se utilizó el principio de Cavalieri. Se utilizó el disector físico para determinar la densidad numérica de las células granulares del giro dentado. Para analizar la morfología de las células granulares del giro dentado se usó la tinción cualitativa de Golgi. Nuestros datos mostraron que el volumen total del hipocampo, el giro dentado y sus subcapas, incluyendo la molecular, granular y polimorfos, en ratones tratados con TiO2, disminuyó significativamente en comparación con el grupo de control. Además, el número total y la densidad numérica de las células de la subcapa granular del giro dentado mostró una reducción significativa en los tres grupos experimentales en comparación con el grupo control. Las células granulares del giro dentado tenían una longitud dendrítica menor y ramas dendríticas disminuidas en los ratones tratados con TiO2 en comparación con los ratones del grupo control. Estos datos pueden justificar los trastornos relacionados con la memoria, el aprendizaje y los daños en las neuronas del hipocampo debido al uso de NP de TiO2.

Animals , Male , Mice , Titanium/pharmacology , Dentate Gyrus/drug effects , Nanoparticles , Hippocampus/drug effects
Int. j. morphol ; 38(6): 1693-1699, Dec. 2020. tab, graf
Article in English | LILACS | ID: biblio-1134500


SUMMARY: Herbal extracts used for treatment of diabetes has focused mostly on the hypoglycaemic and anti-oxidant property.There are no studies which focused on its effect on dendritic architecture of pyramidal neurons of hippocampus caused by diabetes. This study was taken up to explore the effect of administration of Trigonella foenum-graecum (fenugreek) seed extract on diabetes induced dendritic atrophy in hippocampus. Experimental diabetes was induced in rats by administering single dose of Streptozotocin (60 mg/kg)intraperitoneally.Treatment groups of rats were orally administeredfenugreek seed extract of 1 g/kg body weight for 6 weeks. Followingly they were sacrificed and the brains were removed, processed for the Golgi-Cox stain method.The number of dendritic branching points and intersections were counted in successive radial segments of 20 µm up to a radial distance of 100 micron from soma and analysed by the Sholl's method. The rats with diabetes showed a significant decrease in the dendritic length and branching points in most of the apical and basal dendrites of CA1 and CA3 pyramidal neurons.Treatment with fenugreek seed extract were able to significantly alleviate the dendritic atrophy in most of the segments except in the apical branching points of the CA1 neuron. The present study demonstrates that fenugreek seed extract having a proven hypoglycaemic and anti-diabetic property also possess protection to the hippocampal pyramidal neurons form diabetes associated neuronal atrophy.

RESUMEN: Los extractos de hierbas para el tratamiento de la diabetes se han basado principalmente en las propiedades hipoglucémicas y antioxidantes. En la literatura no hay estudios basados en su efecto sobre la arquitectura dendrítica de las neuronas piramidales del hipocampo, causadas por la diabetes. El objetivo de este estudio fue investigar el efecto de la administración de extracto de semilla de Trigonella foenum graecum (fenogreco) sobre la atrofia dendrítica inducida por la diabetes en el hipocampo. Se indujo diabetes experimental en ratas mediante la administración de una dosis única de estreptozotocina (60 mg / kg) por vía intraperitoneal. Se administró a grupos de ratas extracto de semilla de fenogreco a razón de 1 g / kg de peso corporal durante 6 semanas. Las ratas fueron sacrificadas posteriormente y se procesaron los cerebros mediante método de tinción de Golgi-Cox. El número de puntos de ramificación dendrítica e intersecciones se contaron en segmentos radiales sucesivos de 20 µm hasta una distancia radial de 100 micras del soma y se analizaron mediante el método de Sholl. Las ratas con diabetes mostraron una disminución significativa en la longitud dendrítica y los puntos de ramificación en la mayoría de las dendritas apicales y basales de las neuronas piramidales CA1 y CA3. El tratamiento con extracto de semilla de fenogreco alivió significativamente la atrofia dendrítica en la mayoría de los casos, excepto en los puntos de ramificación apical de la neurona CA1. El estudio demuestra que el extracto de semilla de fenogreco además de tener propiedades hipoglucémicas y antidiabéticas, también protege las neuronas piramidales del hipocampo contra la atrofia neuronal asociada a la diabetes.

Animals , Male , Rats , Atrophy/drug therapy , Plant Extracts/administration & dosage , Trigonella/chemistry , Dendrites/drug effects , Diabetes Mellitus, Experimental/drug therapy , Plant Extracts/therapeutic use , Rats, Wistar , Pyramidal Cells , Diabetes Mellitus, Experimental/complications , Hippocampus/drug effects
Electron. j. biotechnol ; 48: 53-61, nov. 2020. ilus, graf
Article in English | LILACS | ID: biblio-1254710


BACKGROUND: Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disease. Recent studies have reported the close association between cognitive function in AD and purinergic receptors in the central nervous system. In the current study, we investigated the effect of CD73 inhibitor α, ß-methylene ADP (APCP) on cognitive impairment of AD in mice, and to explore the potential underlying mechanisms. RESULTS: We found that acute administration of Aß1­42 (i.c.v.) resulted in a significant increase in adenosine release by using microdialysis study. Chronic administration of APCP (10, 30 mg/kg) for 20 d obviously mitigated the spatial working memory impairment of Aß1­42-treated mice in both Morris water maze (MWM) test and Y-maze test. In addition, the extracellular adenosine production in the hippocampus was inhibited by APCP in Aß-treated mice. Further analyses indicated expression of acetyltransferase (ChAT) in hippocampus of mice of was significantly reduced, while acetylcholinesterase (AChE) expression increased, which compared to model group. We observed that APCP did not significantly alter the NLRP3 inflammasome activity in hippocampus, indicating that anti-central inflammation seems not to be involved in APCP effect. CONCLUSIONS: In conclusion, we report for the first time that inhibition of CD73 by APCP was able to protect against memory loss induced by Aß1­42 in mice, which may be due to the decrease of CD73-driven adenosine production in hippocampus. Enhancement of central cholinergic function of the central nervous system may also be involved in the effects of APCP.

Animals , Male , Mice , Adenosine Diphosphate/analogs & derivatives , Neurodegenerative Diseases/prevention & control , Hippocampus , Nucleotidases/antagonists & inhibitors , Acetylcholinesterase , Adenosine Diphosphate/administration & dosage , Alzheimer Disease/prevention & control , Morris Water Maze Test , Mice, Inbred C57BL
Int. j. med. surg. sci. (Print) ; 7(2): 1-14, jun. 2020. ilus, tab, graf
Article in English | LILACS | ID: biblio-1179239


Introduction: Aluminium, a ubiquitous metal implicated in some neurodegenerative diseases is linked to activation of free oxygen species. The antioxidant-rich plants, Moringa oleifera (MO) is reported to protect against Aluminium activities. This study investigated the actions of MO leaf extract (MOLE) against Aluminium chloride (AlCl3)- induced hippocampal cellular changes and serum levels of alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) in adult Wistar rats.Materials and Methods: Thirty Wistar rats weighing between 150 g and 220 g were grouped (n=5) into; 1-control (5 mL/kg distilled water), 2-AlCl3 (100 mg/kg), 3-low dose MOLE (250 mg/kg), 4-high dose MOLE (1,000 mg/kg), 5-concurrent AlCl3 and low dose MOLE, and 6-concurrent AlCl3 and high dose MOLE. All administrations were by oral gavages for 21 days. On day 22, following deep anaesthesia and cardiac puncture, blood was obtained for serum enzyme analysis, and the brain perfusion fixed, harvested and processed for histological study.Results: Results showed significantly (p < 0.05) higher ALP level in the AlCl3 group compared with the control, as well as the other test groups. However, there was no significant (p > 0.05) AST and ALT levels. The hippocampal CA3 of the AlCl3 group showed hypertrophic cells, with some of the cells having karyorrhectic features. The concurrent AlCl3 and low and high doses, MOLE groups showed less of these adverse features.Conclusion: These results suggest that MOLE may protect enzymatic activities against Aluminium chloride. However, its action on hippocampus is still subject to further investigation.

Introducción: El aluminio, un metal presente en diversos lugares implicado en algunas enfermedades neurodegenerativas, está relacionado con la activación de especies reactivas de oxígeno. Se informa que las plantas ricas en antioxidantes, Moringa oleifera (MO) protegen contra la acción del aluminio. Este estudio investigó las acciones del extracto de hoja de MO (MOLE) en los cambios celulares del hipocampo inducidos por el cloruro de aluminio (AlCl3) y los niveles séricos de fosfatasa alcalina (ALP), aspartato transaminasa (AST) y alanina transaminasa (ALT) en ratas Wistar adultas.Materiales y métodos: SE utilizaron treinta ratas Wistar divididas en 5 grupos, los animales pesaban entre 150 gy 220 g; 1 control (5 ml / kg de agua destilada), 2-AlCl3 (100 mg / kg), 3 MOLE de dosis baja (250 mg / kg), 4 MOLE de dosis alta (1000 mg / kg), 5 AlCl3 concurrente y MOLE de dosis baja, y MOLE 6-concurrente y MOLE de dosis alta. Todas las administraciones fueron por sonda oral durante 21 días. El día 22, después de la anestesia profunda y la punción cardíaca, se obtuvo sangre para el análisis de las enzimas séricas y la perfusión cerebral se fijó, recogió y procesó para el estudio histológico.Resultados: Los resultados mostraron un nivel de ALP significativamente (p <0.05) más alto en el grupo AlCl3 en comparación con el control, así como en los otros grupos de prueba. Sin embargo, no hubo niveles significativos (p> 0.05) de AST y ALT. El hipocampo CA3 del grupo AlCl3 mostró células hipertróficas, y algunas de las células tenían características cariorrecticas. Los grupos de AlCl3 concurrentes y dosis bajas y altas, MOLE mostraron menos de estas características adversas.Conclusión: Estos resultados sugieren que MOLE puede proteger las actividades enzimáticas contra el cloruro de aluminio. Sin embargo, su acción sobre el hipocampo aún está sujeta a más investigaciones.

Animals , Rats , Moringa oleifera/anatomy & histology , Aluminum Chloride/administration & dosage , Hippocampus/anatomy & histology , Rats, Wistar
Int. j. med. surg. sci. (Print) ; 7(2): 1-19, jun. 2020. graf, ilus
Article in English | LILACS | ID: biblio-1179247


Rauwolfia vomitoria Afzel. is an antipsychotic plant used by several African communities in the management of psychiatric conditions with good outcomes. Concerns about its dosages on brain activity lead to this investigation of its action on the hippocampal microstructure.Twenty-four adult male Wistar rats of average weight 200 g, were assigned into four groups (n = 6): control; 200, 300 and 400 mg/kg body weight of RVroot bark extract, respectively. The administration was once daily, and orally for seven days. Daily observation of the animals was done till on day eight when they were sacrificed after deep anaesthesia. Each brain was processed for histology and immunohistochemical studies. Animals in the 200, 300 and 400 mg/kg RV groups appeared generally dull and drowsy, and barely fed. Their hippocampal histology showed neuronal atrophy and karyorrhexis, with no difference in cell count, although the pyramidal cell numbers decreased in the 300 and 400 mg/kg RV groups. Neuron-specific enolase decreased in the 400 mg/kg RV group, while neurofilament decreased in all test groups. Glial fibrillary acidic protein expression and density increased in the 200 and 300 mg/kg RV groups, but not the 400 mg/kg RV group, all compared with the control group.The given doses of RV root bark extractin adult Wistar rats showed sedative activities with hippocampal histopathological changes, which may not be reversible, thereby leading to the hippocampal functional deficit.

Introducción: Rauwolfia vomitoria (RV) Afzel es una planta antipsicótica utilizada por varias comunidades africanas en el tratamiento de enfermedades psiquiátricas con buenos resultados. Las preocupaciones sobre sus efecto sobre la actividad cerebral conducen a esta investigación de su acción sobre la microestructura del hipocampo.Materiales y métodos: Se asignaron veinticuatro ratas Wistar macho adultas de un peso medio de 200 g, en cuatro grupos (n = 6): control; 200, 300 y 400 mg / kg de peso corporal de extracto de corteza de raíz de RV, respectivamente. La administración fue una vez al día y por vía oral durante siete días. Se realizó una observación diaria de los animales hasta el día ocho, cuando fueron sacrificados después de una anestesia profunda. Cada cerebro fue procesado para estudios histológicos e inmunohistoquímicos.Resultados: Los animales en los grupos de RV de 200, 300 y 400 mg / kg parecían generalmente apagados y somnolientos, y apenas alimentados. Su histología hipocampal mostró atrofia neuronal y cariorrexis, sin diferencia en el recuento celular, aunque el número de células piramidales disminuyó en los grupos de RV de 300 y 400 mg / kg. La enolasa específica de neuronas disminuyó en el grupo de RV de 400 mg / kg, mientras que el neurofilamento disminuyó en todos los grupos de prueba. La expresión y densidad de la proteína fibrilar ácida glial aumentó en los grupos de RV de 200 y 300 mg / kg, pero no en el grupo de RV de 400 mg / kg, todos en comparación con el grupo de control.Conclusión: Las dosis administradas de extracto de corteza de raíz de RV en ratas Wistar adultas mostraron actividades sedantes, con cambios histopatológicos del hipocampo, que pueden no ser reversibles, lo que conduce al déficit funcional del hipocampo.

Animals , Rats , Rauwolfia/chemistry , Plant Extracts/therapeutic use , Hippocampus/anatomy & histology , Rats, Wistar
Rev. bras. neurol ; 56(2): 46-52, abr.-jun. 2020. ilus, tab
Article in English | LILACS | ID: biblio-1103037


The nature of memory and the search for its localization have been a subject of interest since Antiquity. After millennia of hypothetical concepts the core memory-related structures finally began to be identified through modern scientifically-based methods at the diencephalic, hippocampal, and neocortical levels. However, there was a clear temporal delay between the finding of these anatomic structures ignoring their function, and their identification related to memory function. Thus, the core structures begun to be identified with a pure anatomical view in the late Middle Ages on, while the memory function related to them was discovered much later, in the late Modern Period.

A natureza da memória e a busca de sua localização tem sido objeto de interesse desde a Antiguidade. Após milênios de conceitos hipotéticos as estruturas centrais relacionadas com a memória finalmente começaram a ser identificadas através de métodos modernos com base científica, nos níveis diencefálico, hipocampal e neocortical. Entretanto, houve um claro retardo temporal entre o achado dessas estruturas anatômicas ignorando sua função e sua identificação relacionada à função da memória. Assim, as estruturas centrais começaram a ser identificadas com uma visão puramente anatômica da Idade Média tardia em diante, enquanto a função da memória relacionada com as mesmas foi descoberta muito mais tarde, no Período Moderno tardio.

Humans , History, 19th Century , History, 20th Century , Cerebral Cortex/anatomy & histology , Cerebrum/anatomy & histology , Memory/physiology , Neocortex , Diencephalon , Hippocampus
Int. j. morphol ; 38(2): 400-405, abr. 2020. graf
Article in English | LILACS | ID: biblio-1056454


Accumulating evidence from preclinical and clinical studies indicates prenatal exposure to stress or excess glucocorticoids can affect offspring brain. Glucocorticoid receptor (GR) is an important target of glucocorticoid. Therefore the aim of the present study was to investigate the expression of GR in prenatally stressed adult offspring and the relationship between GR expression and behavior in offspring. Pregnant rats received restraint stress during the last week of pregnancy. Hippocampal glucocorticoid receptor expression levels in the offspring were detected on postnatal 60 (P60).Cognition function was also detected. It shows significantly lower hippocampal GR expression was observed in female prenatally stressed offspring compared with their controls at P60. Corresponding to the expression of GR, female prenatally stressed offspring exhibited poorer spatial learning and memory abilities in the Barnes maze than control, This suggests that cognitive impairment in prenatally stressed rat offspring attribute lower hippocampal GR expression.

La evidencia acumulada de estudios preclínicos y clínicos indica que la exposición prenatal al estrés, o el exceso de glucocorticoides puede afectar el desarrollo cerebral de las crías. El receptor de glucocorticoides (RG) es un objetivo importante de los glucocorticoides. Por lo tanto, el objetivo del presente estudio fue investigar la expresión de RG en crías adultas estresadas durante el período prenatal y la relación entre la expresión de RG y el comportamiento de las crías. Las ratas preñadas recibieron niveles de estrés restringido, durante la última semana de embarazo. Se determinaron niveles de expresión del receptor de glucocorticoides del hipocampo y niveles de función cognitiva en las crías. En comparación con el grupo control se observó una expresión de RG en el hipocampo, significativamente menor en las crías estresadas prenatalmente, en comparación con los controles en P60. En referencia a la expresión de RG, las crías estresadas prenatalmente exhibieron habilidades de memoria y aprendizaje espacial menores, en el laberinto de Barnes que el grupo control. Esto sugiere que el deterioro cognitivo en crías de ratas estresadas prenatalmente muestran una menor expresión de RG en el hipocampo.

Animals , Female , Pregnancy , Rats , Prenatal Exposure Delayed Effects , Receptors, Glucocorticoid/metabolism , Cognitive Dysfunction , Hippocampus/metabolism , Stress, Physiological , Immunohistochemistry , Blotting, Western , Rats, Sprague-Dawley