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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. j. med. biol. res ; 54(2): e10107, 2021. graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1142578


Ketamine (KET) is an N-methyl-D-aspartate (NMDA) antagonist with rapid and long-lasting antidepressant effects, but how the drug shows its sustained effects is still a matter of controversy. The objectives were to evaluate the mechanisms for KET rapid (30 min) and long-lasting (15 and 30 days after) antidepressant effects in mice. A single dose of KET (2, 5, or 10 mg/kg, po) was administered to male Swiss mice and the forced swim test (FST) was performed 30 min, 15, or 30 days later. Imipramine (IMI, 30 mg/kg, ip), a tricyclic antidepressant drug, was used as reference. The mice were euthanized, separated into two time-point groups (D1, first day after KET injection; D30, 30 days later), and brain sections were processed for glycogen synthase kinase-3 (GSK-3), histone deacetylase (HDAC), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) immunohistochemical assays. KET (5 and 10 mg/kg) presented rapid and long-lasting antidepressant-like effects. As expected, the immunoreactivities for brain GSK-3 and HDAC decreased compared to control groups in all areas (striatum, DG, CA1, CA3, and mainly pre-frontal cortex, PFC) after KET injection. Increases in BDNF immunostaining were demonstrated in the PFC, DG, CA1, and CA3 areas at D1 and D30 time-points. GFAP immunoreactivity was also increased in the PFC and striatum at both time-points. In conclusion, KET changed brain BDNF and GFAP expressions 30 days after a single administration. Although neuroplasticity could be involved in the observed effects of KET, more studies are needed to explain the mechanisms for the drug's sustained antidepressant-like effects.

Animals , Male , Rabbits , Brain/drug effects , Brain/enzymology , Brain-Derived Neurotrophic Factor/metabolism , Ketamine/pharmacology , Antidepressive Agents/pharmacology , Astrocytes , Glycogen Synthase Kinase 3 , Disease Models, Animal , Glial Fibrillary Acidic Protein , Histone Deacetylases
Acta Physiologica Sinica ; (6): 223-232, 2021.
Article in English | WPRIM | ID: wpr-878251


The present study was aimed to investigate the role of GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus (CSF-CN) in neuropathic pain. Intra-lateral ventricle injection of cholera toxin subunit B conjugated with horseradish peroxidase (CBHRP) was used to label the CSF-CN. Double-labeled immunofluorescent staining and Western blot were used to observe the expression of GluN2B and BDNF in the CSF-CN. Chronic constriction injury of sciatic nerve (CCI) rat model was used to duplicate the neuropathic pain. Pain behavior was scored to determine the analgesic effects of GluN2B antagonist Ro 25-6981 and BDNF neutralizing antibody on CCI rats. GluN2B and BDNF were expressed in the CSF-CN and their expression was up-regulated in CCI rats. Intra-lateral ventricle injection of GluN2B antagonist Ro 25-6981 or BDNF neutralizing antibody notably alleviated thermal hyperalgesia and mechanical allodynia in CCI rats. Moreover, the increased expression of BDNF protein in CCI rats was reversed by intra-lateral ventricle injection of Ro 25-6981. These results suggest that GluN2B and BDNF are expressed in the CSF-CN and alteration of GluN2B-BDNF pathway in the CSF-CN is involved in the modulation of the peripheral neuropathic pain.

Animals , Brain-Derived Neurotrophic Factor , Hyperalgesia , Neuralgia , Rats , Rats, Sprague-Dawley , Sciatic Nerve
Arq. bras. cardiol ; 115(2): 263-269, ago., 2020. graf
Article in English, Portuguese | SES-SP, LILACS, SES-SP | ID: biblio-1131300


Resumo As doenças cardiovasculares (DCV) são atualmente a maior causa de morte no Brasil e no mundo. Em 2016 as DCV foram responsáveis por mais de 17 milhões de mortes, representando 31% de todas as mortes em nível global. Mecanismos moleculares e genéticos podem estar envolvidos na proteção cardiovascular e devem ser considerados nas novas abordagens terapêuticas. Nesse sentido, recentes estudos têm relatado que o Fator Neurotrófico Derivado do Encéfalo (Brain-Derived Neurotrophic Factor, BDNF) está reduzido em indivíduos predispostos a desenvolverem DCV, e que o treinamento físico aeróbio aumenta as quantidades de BDNF circulante. O BDNF é uma neurotrofina encontrada em altas concentrações no hipocampo e córtex cerebral, sendo considerada molécula-chave na manutenção da plasticidade sináptica e na sobrevivência das células neuronais. Além da plasticidade neuronal, BDNF também é importante na função vascular, promovendo angiogênese por meio da regulação por espécies reativas de oxigênio (ROS). Entretanto, uma variante do gene do BDNF em humanos, o polimorfismo Val66Met (substituição do aminoácido valina por uma metionina na posição 66 do códon), que ocorre em 20-30% da população caucasiana, pode afetar as concentrações de BDNF no plasma e sua atividade em todos os tecidos periféricos contendo receptores tirosina quinase B (TrkB), como o endotélio. De fato, recentemente observamos que o polimorfismo Val66Met prejudica a reatividade vascular e o BDNF circulante em resposta ao treinamento físico. Dessa forma, apresentaremos a seguir uma discussão sobre os níveis séricos de BDNF na proteção cardiovascular, a variante genética Val66Met na reatividade vascular e o efeito do exercício físico.

Abstract Cardiovascular disease (CVD) is currently the leading cause of death in Brazil and worldwide. In 2016, CVD accounted for more than 17 million deaths, representing 31% of all deaths globally. Molecular and genetic mechanisms may be involved in vascular protection and should be considered in new therapeutic approaches. In this sense, recent studies have reported that brain-derived neurotrophic factor (BDNF) is reduced in individuals predisposed to develop CVD, and that aerobic physical training increases the amounts of circulating BDNF. BDNF is a neurotrophin found at high concentrations in the hippocampus and cerebral cortex and is considered a key molecule for the maintenance of synaptic plasticity and survival of neuronal cells. In addition to neuronal plasticity, BDNF is also important in vascular function, promoting angiogenesis through the regulation of reactive oxygen species (ROS). However, a variant of the BDNF gene in humans, the Val66Met polymorphism (substitution of the amino acid valine for a methionine at position 66 of the codon), occurring in 20-30% of the Caucasian population, may affect plasma BDNF concentrations and its activity in all peripheral tissues containing tyrosine kinase B receptors (TrkB), such as the endothelium. Thus, we will present a discussion about the role of serum BDNF levels in cardiovascular protection, Val66Met genetic variant in vascular reactivity and the effect of physical exercise.

Humans , Exercise , Brain-Derived Neurotrophic Factor/genetics , Valine , Brazil , Methionine
Dement. neuropsychol ; 14(1): 41-46, Jan.-Mar. 2020. tab
Article in English | LILACS | ID: biblio-1089810


ABSTRACT A few studies have shown that serum brain-derived neurotrophic factor (BDNF) level in post-stroke depression is highly correlated with memory and neuropsychiatric disturbances. Objective: This study aimed to elucidate the relationship of serum BDNF, malondialdehyde (MDA), and 8-Hydroxy 2-Deoxyguanosine (8-OhdG) levels in acute stroke cases with one-month post-stroke depression. Methods: An observational study was conducted of 72 post-ischemic stroke patients in the Neurology ward of the Dr. M. Djamil Hospital, Padang, West Sumatra, Indonesia. Acute stroke (< 48 hours) serum BDNF, MDA, and 8-OhdG levels were measured using ELISA. Based on observations using the Hamilton Depression Rating Scale conducted one month after stroke, respondents were divided into two groups: with and without depression. The mean serum level was analyzed using the t-test and Mann-Whitney test, while differences in basic characteristics were analyzed using the Chi-square test. Multivariate analysis was conducted to determine the most significant factor associated with post-stroke depression. The error rate was set at 5%. Results: BDNF levels in acute stroke were significantly lower in the depression group than in the non-depression group (p < 0.05). MDA and 8-OhdG levels in acute stroke were higher in the depression group (p < 0.05). BDNF level during acute stroke was negatively correlated with post-stroke depression, while, conversely, acute stroke MDA and 8-OhdG levels were positively correlated with depression. Conclusion: BDNF had a negative correlation, while MDA and 8-OhdG had a positive correlation, with depression one-month post-stroke. 8-OhdG was the most influential factor in post-stroke depression.

RESUMO Alguns estudos mostraram que o nível sérico de fator neurotrófico derivado do cérebro (BDNF) na depressão pós-AVC está altamente correlacionado com a memória e com os distúrbios neuropsiquiátricos. Objetivo: Este estudo teve como objetivo elucidar a relação entre os níveis séricos de BDNF, malondialdeído (MDA) e 8-hidroxi 2-desoxiganosanos (8 OhdG) em casos de AVC agudo com depressão pós-AVC de um mês. Métodos: Um estudo observacional foi realizado em 72 pacientes com AVC pós-isquêmico na enfermaria de Neurologia do Hospital Dr. M. Djamil, Padang, Sumatra Ocidental, Indonésia. Os níveis séricos de BDNF, MDA e 8-OhdG no AVC agudo (< 48 horas) foram medidos usando ELISA. Com base nas observações da Hamilton Depression Rating Scale realizada um mês após o AVC, os entrevistados foram divididos em dois grupos: com e sem depressão. O nível sérico médio foi analisado pelo teste T e Mann-Whitney, enquanto as diferenças nas características básicas foram analisadas pelo teste do qui-quadrado. A análise multivariada foi realizada para determinar o fator mais significativo associado à depressão pós-AVC. A taxa de erro foi fixada em 5%. Resultados: O nível de BDNF no AVC agudo foi significativamente menor na depressão do que no grupo sem depressão (p < 0,05). Os níveis de MDA e 8-OhdG no AVC agudo foram maiores no grupo de depressão (p < 0,05). O nível de BDNF durante o AVC agudo foi negativamente correlacionado com os casos de depressão pós-AVC, enquanto, inversamente, os níveis de MDA e 8-OhdG do AVC agudo foram positivamente correlacionados com os casos de depressão. Conclusão: O BDNF tem uma correlação negativa, enquanto o MDA e o 8-OhdG tiveram uma correlação positiva com a depressão um mês após o AVC. 8-OhdG foi o fator mais influente na depressão pós-AVC.

Humans , Brain-Derived Neurotrophic Factor , Stroke , Depression , Ischemia , Malondialdehyde
Chonnam Medical Journal ; : 20-26, 2020.
Article in English | WPRIM | ID: wpr-787278


We examined the effect of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on neuronal viability in mouse cortical near-pure neuronal cultures. Addition of fluoxetine to the media for 24 hours induced neuronal death in a concentration-dependent manner. To delineate the mechanisms of fluoxetine-induced neuronal death, we investigated the effects of trolox, cycloheximide (CHX), BDNF, z-VAD-FMK, and various metal-chelators on fluoxetine-induced neuronal death. Neuronal death was assessed by MTT assay. The addition of 20 µM fluoxetine to the media for 24 hours induced 60–70% neuronal death, which was associated with the hallmarks of apoptosis, chromatin condensation and DNA laddering. Fluoxetine-induced death was significantly attenuated by CHX, BDNF, or z-VAD-FMK. Treatment with antioxidants, trolox and ascorbate, also markedly attenuated fluoxetine-induced death. Interestingly, some divalent cation chelators (EGTA, Ca-EDTA, and Zn-EDTA) also markedly attenuated the neurotoxicity. Fluoxetine-induced reactive oxygen species (ROS) generation was measured using the fluorescent dye 2′,7′-dichlorofluorescin diacetate. Trolox and bathocuproine disulfonic acid (BCPS), a cell membrane impermeable copper ion chelator, markedly attenuated the ROS production and neuronal death. However, deferoxamine, an iron chelator, did not affect ROS generation or neurotoxicity. We examined the changes in intracellular copper concentration using a copper-selective fluorescent dye, Phen Green FL, which is quenched by free copper ions. Fluoxetine quenched the fluorescence in neuronal cells, and the quenching effect of fluoxetine was reversed by co-treatment with BCPS, however, not by deferoxamine. These findings demonstrate that fluoxetine could induce apoptotic and oxidative neuronal death associated with an influx of copper ions.

Animals , Antioxidants , Apoptosis , Brain-Derived Neurotrophic Factor , Cell Death , Cell Membrane , Chelating Agents , Chromatin , Copper , Cycloheximide , Deferoxamine , DNA , Fluorescence , Fluoxetine , Ions , Iron , Mice , Neurons , Reactive Oxygen Species , Serotonin
Article in English | WPRIM | ID: wpr-787141


Neuroinflammation is an important process underlying a wide variety of neurodegenerative diseases. Carvacrol (CAR) is a phenolic monoterpene commonly used as a food additive due to its antibacterial properties, but it has also been shown to exhibit strong antioxidative, anti-inflammatory, and neuroprotective effects. Here, we sought to investigate the effects of CAR on inflammation in the hippocampus and prefrontal cortex, as well as the molecular mechanisms underlying these effects. In our study, lipopolysaccharide was injected into the lateral ventricle of rats to induce memory impairment and neuroinflammation. Daily administration of CAR (25, 50, and 100 mg/kg) for 21 days improved recognition, discrimination, and memory impairments relative to untreated controls. CAR administration significantly attenuated expression of several inflammatory factors in the brain, including interleukin-1β, tumor necrosis factor-α, and cyclooxygenase-2. In addition, CAR significantly increased expression of brain-derived neurotrophic factor (BDNF) mRNA, and decreased expression of Toll-like receptor 4 (TLR4) mRNA. Taken together, these results show that CAR can improve memory impairment caused by neuroinflammation. This cognitive enhancement is due to the anti-inflammatory effects of CAR medicated by its regulation of BDNF and TLR4. Thus, CAR has significant potential as an inhibitor of memory degeneration in neurodegenerative diseases.

Animals , Brain , Brain-Derived Neurotrophic Factor , Cyclooxygenase 2 , Cytokines , Discrimination, Psychological , Food Additives , Hippocampus , Inflammation , Lateral Ventricles , Lipopolysaccharides , Memory , Necrosis , Neurodegenerative Diseases , Neuroprotective Agents , Phenol , Prefrontal Cortex , Rats , RNA, Messenger , Toll-Like Receptor 4
Braz. j. med. biol. res ; 53(10): e9861, 2020. graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1132476


Fetal exposure to sevoflurane induces long-term cognitive impairment. Histone acetylation regulates the transcription of genes involved in memory formation. We investigated whether sevoflurane exposure during late-pregnancy induces neurocognitive impairment in offspring, and if this is related to histone acetylation dysfunction. We determined whether the effects could be reversed by an enriched environment (EE). Pregnant rats were exposed to 2.5% sevoflurane or control for 1, 3, or 6 h on gestational day 18 (G18). Sevoflurane reduced brain-derived neurotrophic factor (BDNF), acetyl histone H3 (Ac-H3), and Ac-H4 levels and increased histone deacetylases-2 (HDAC2) and HDAC3 levels in the hippocampus of the offspring on postnatal day 1 (P1) and P35. Long-term potentiation was inhibited, and spatial learning and memory were impaired in the 6-h sevoflurane group at P35. EE alleviated sevoflurane-induced cognitive dysfunction and increased hippocampal BDNF, Ac-H3, and Ac-H4. Exposure to 2.5% sevoflurane for 3 h during late-pregnancy decreased hippocampal BDNF, Ac-H3, and Ac-H4 in the offspring but had no effect on cognitive function. However, when the exposure time was 6 h, impaired spatial learning and memory were linked to reduced BDNF, Ac-H3, and Ac-H4, which could be reversed by EE.

Animals , Female , Pregnancy , Rats , Cognitive Dysfunction , Acetylation , Histones , Maze Learning , Brain-Derived Neurotrophic Factor , Sevoflurane , Hippocampus
Rev Assoc Med Bras (1992) ; 66(5): 615-622, 2020. tab
Article in English | SES-SP, LILACS, SES-SP | ID: biblio-1136248


SUMMARY OBJECTIVE To explore the association of brain-derived neurotrophic factor gene (BDNF) polymorphism with the latent cognitive endophenotype of posttraumatic stress disorder (PTSD) after major natural disasters in Hainan Province, China. METHODS A total of 300 patients with PTSD and 150 healthy controls (HC) were surveyed by psychoanalysis scale to assess their cognitive functions. Polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) were used to detect the BDNF gene polymorphism. RESULTS In terms of the cognitive function, the scores in the PTSD group were worse than those of the HC group (P < 0.05 or P < 0.01). There was a significant difference in the distribution of BDNF genotype and allele frequency between the two groups (P < 0.05). PTSD endophenotypes were significantly different among the BDNF genotypes in the PTSD group (P ≤ 0.01). CONCLUSION There is a statistically significant difference in the polymorphism of BDNF gene between PTSD and HC groups, and the alleles are associated with the incidence of PTSD. Thus, it may be a risk factor for PTSD.

RESUMO OBJETIVO Explorar a associação do polimorfismo do gene fator neurotrófico derivado do cérebro (BDNF) com o endofenótipo cognitivo latente de transtorno de estresse pós-traumático (TEPT) após grandes desastres naturais na província de Hainan, China. MÉTODOS Um total de 300 doentes com TEPT e 150 controles saudáveis (HC) foi investigado pela escala de psicanálise para avaliar as suas funções cognitivas. A reação em cadeia polimerase (PCR) e a eletroforese em gel de poliacrilamida (Page) foram usadas para detectar o polimorfismo do gene BDNF. RESULTADOS Em termos de função cognitiva, as pontuações no grupo TEPT foram piores do que as do grupo HC (P<0,05 ou P<0,01). Houve uma diferença significativa na distribuição do genótipo de BDNF e frequência do alelo entre os dois grupos (P<0,05). Os endofenótipos de TEPT foram significativamente diferentes entre os genótipos de BDNF do grupo TEPT (P≤0,01). CONCLUSÃO Existe uma diferença estatisticamente significativa no polimorfismo do gene BDNF entre o TEPT e os grupos HC, e os alelos estão associados à incidência do TEPT. Assim, pode ser um fator de risco para TEPT.

Humans , Brain-Derived Neurotrophic Factor/genetics , Polymorphism, Genetic , Stress Disorders, Post-Traumatic , China , Polymorphism, Single Nucleotide , Alleles , Endophenotypes , Genotype
Article in Chinese | WPRIM | ID: wpr-826380


To investigate the association between chronic unpredictable mild stress (CUMS)-induced depressive-like behavior in rats and expressions of brain-derived neurotrophic factor (BDNF) and S100β in the hippocampal and prefrontal cortex. Rats were randomly assigned to three groups:saline control group,saline+CUMS group,and citalopram +CUMS group. CUMS was used for depression modeling in rats. Depressive-like behavior in rats were evaluated by open-field test,sucrose preference test,and novel object recognition test. S100β and BDNF expressions were tested by enzyme-linked immunosorbent assay. Rats in the saline+CUMS group had significantly lower score in sucrose preference [(52.48±13.14)%],basic motor tasks [(845.8±371.4)s],fine motor tasks [(565.6±211.9)s],and longer resting time [(282.6±11.8)s] compared to the control group [(84.30±6.15)% (=7.49,=0.000),(1239.1±281.6)s (=2.83,=0.008),(801.8±150.9)s (=3.05,=0.003),(268.2±12.8)s (=2.72,=0.001)]. Compared with the citalopram+CUMS group,rats from the saline+CUMS group also showed significantly lower results in sucrose preference [(80.55±11.31)%,=5.39,=0.000],basic motor tasks [(1156.4±314.7)s,=2.13,=0.031],and fine motor tasks [(736.1±150.0)s,=2.21,=0.008]. There were no significant differences in the expression of hippocampal and prefrontal BDNF between these two groups,but rats from the saline+CUMS group expressed significantly higher levels of S100β compared to rats from the citalopram+CUMS group [(13.22±2.23) ng/g (10.55±2.72) ng/g,=2.67,=0.014]. Pearson correlation analysis revealed that the expression of S100β was positively correlated with the expression of BDNF in the prefrontal cortex and hippocampus (=0.35,=0.034;=0.36,=0.034).The novel object recognition index was positively correlated with the expression of BDNF in the hippocampus(=0.38,=0.021),and the duration of fine-motor activities was negatively correlated with S100β in the prefrontal cortex (=-0.36,=0.037). Different types of depressive behaviors in rats induced by CUMS are associated with the selective expression of S100β and BDNF in two different brain cortex. S100β protein and BDNF may independently participate in the pathogenesis of depression.

Animals , Antidepressive Agents , Brain-Derived Neurotrophic Factor , Metabolism , Citalopram , Depression , Metabolism , Disease Models, Animal , Frontal Lobe , Metabolism , Hippocampus , Metabolism , Random Allocation , Rats , S100 Calcium Binding Protein beta Subunit , Metabolism , Stress, Psychological
Arq. neuropsiquiatr ; 77(12): 881-887, Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1055207


ABSTRACT Induction of long-term potentiation (LTP) increases the storage capacity of synapses in the hippocampal dentate gyrus (DG). Irisin is a myokine generated from FNDC5 (a gene precursor) during exercise. Although intra-cornu ammonis 1 administration of irisin fortifies LTP in mice with Alzheimer's disease, the effects of intra-DG injection of irisin on the LTP in rats remains to be elucidated in vivo. In this study, male Wistar rats were randomly divided into a control group (saline), irisin (0.5, 1, and 1.5 μg/rat), and dimethyl sulfoxide (DMSO). After treatment, the population spike (PS) amplitude and slope of excitatory postsynaptic potentials (EPSP) were measured in the DG of rats in vivo. Moreover, following completion of the experiments, the stimulating and recording sites in the hippocampus were confirmed histologically from brain sections. Furthermore, biochemical assays like malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidant status (TOS) were evaluated (the antioxidant markers were analyzed in the plasma). Our results suggest that all doses of irisin (0.5, 1, 1.5 μg/rat) caused an increase in the EPSP slope and PS amplitude when compared with the control group. In addition, the results obtained showed that irisin decreased TOS and MDA levels while increasing TAC levels as a marker of lipid peroxidation in plasma. The present report provides direct evidence that irisin affects the activity-dependent synaptic plasticity in the dentate gyrus.

RESUMO A indução de potenciação de longo prazo (LTP) aumenta a capacidade de armazenamento das sinapses no giro denteado (DG) do hipocampo. A irisina é uma miocina gerada a partir do FNDC5 (um precursor genético) durante o exercício. Embora a administração intra-Cornu Ammonis1 de irisina fortaleça a LTP em camundongos com doença de Alzheimer, os efeitos da injeção intra-denteada de irisina sobre a LTP em ratos ainda precisam ser elucidados in vivo. Neste estudo, ratos Wistar machos foram divididos aleatoriamente em um grupo controle (solução salina), irisina (0,5, 1 e 1,5 μg / rato) e dimetilsulfóxido (DMSO). Após o tratamento, a amplitude do pico populacional (PS) e a variação dos potenciais pós-sinápticos excitatórios (EPSP) foram medidos no DG de ratos in vivo. Além disso, após a conclusão das experiências, os locais de estimulação e registro no hipocampo foram confirmados histologicamente a partir de secções do cérebro. Adicionalmente, ensaios bioquímicos como malondialdeído (MDA), capacidade antioxidante total (TAC) e status oxidante total (TOS) foram avaliados (os marcadores antioxidantes foram analisados no plasma). Nossos resultados sugerem que todas as doses de irisina (0,5, 1, 1,5 μg / rato) causaram um aumento na variação da EPSP e na amplitude da PS quando comparadas com o grupo controle. Além disso, os resultados obtidos mostraram que a irisina diminuiu os níveis de TOS e MDA, enquanto aumentou os níveis de TAC como um marcador da peroxidação lipídica no plasma. O presente estudo fornece evidências diretas de que a irisina afeta a plasticidade sináptica dependente de atividade no DG.

Animals , Male , Neuropeptides/administration & dosage , Fibronectins/administration & dosage , Long-Term Potentiation/drug effects , Dentate Gyrus/drug effects , Microinjections/methods , Reference Values , Time Factors , Lipid Peroxidation , Random Allocation , Reproducibility of Results , Rats, Wistar , Brain-Derived Neurotrophic Factor/analysis , Brain-Derived Neurotrophic Factor/drug effects , Excitatory Postsynaptic Potentials/drug effects , Malondialdehyde/blood , Antioxidants/analysis
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 41(5): 419-427, Sept.-Oct. 2019. tab, graf
Article in English | LILACS | ID: biblio-1039115


Objective: To evaluate whether an animal model of mania induced by lisdexamfetamine dimesylate (LDX) has an inflammatory profile and whether immune activation by lipopolysaccharides (LPS) has a cumulative effect on subsequent stimuli in this model. We also evaluated the action of lithium (Li) on inflammatory and neurotrophic factors. Methods: Adult male Wistar rats were subjected to an animal model of mania. After the open-field test, they were given LPS to induce systemic immune activation. Subsequently, the animals' blood was collected, and their serum levels of brain-derived neurotrophic factor and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1β, IL-10, and inducible nitric oxide synthase [iNOS]) were measured. Results: LDX induced hyperactivity in the animals, but no inflammatory marker levels increased except brain-derived neurotrophic factor (BDNF). Li had no effect on serum BDNF levels but prevented iNOS levels from increasing in animals subjected to immune activation. Conclusion: Although Li prevented an LPS-induced increase in serum iNOS levels, its potential anti-inflammatory effects in this animal model of mania were conflicting.

Animals , Male , Bipolar Disorder/immunology , Disease Models, Animal , Lisdexamfetamine Dimesylate , Lithium/pharmacology , Anti-Inflammatory Agents/pharmacology , Nerve Growth Factors/drug effects , Time Factors , Bipolar Disorder/physiopathology , Bipolar Disorder/chemically induced , Enzyme-Linked Immunosorbent Assay , Lipopolysaccharides/pharmacology , Reproducibility of Results , Cytokines/blood , Treatment Outcome , Rats, Wistar , Brain-Derived Neurotrophic Factor/blood , Nitric Oxide Synthase Type II/blood , Locomotion/drug effects
Trends psychiatry psychother. (Impr.) ; 41(3): 237-246, July-Sept. 2019. tab
Article in English | LILACS | ID: biblio-1043526


Abstract Objective To assess the association between brain-derived neurotrophic factor (BDNF) levels and acute stress disorder (ASD) in patients who have suffered physical trauma. Methods Data were collected at an emergency hospital in Porto Alegre, state of Rio Grande do Sul, southern Brazil. Participants were over 18 years of age, victims of physical trauma, and had been hospitalized for a minimum of 48 hours. A total of 117 hospitalized patients who agreed to participate in the research were grouped according to the shift in which blood was collected (38 subjects from the morning shift and 79 from the afternoon shift), had their BDNF levels measured and responded to other questionnaires. Respondents were further grouped by age into three ranges: 18-30, 31-50 and 51-70 years. Results We found a significant difference in the distribution of BDNF between the two shifts in which blood samples were collected, with the afternoon group having higher BDNF levels (U = 1906.5, p = 0.018). A difference was observed only between the 18-30 group and the 51-70 group in the afternoon shift (Umorning = 1107, pmorning = 0.575; Uafternoon = 7175, pafternoon = 0.028). Conclusions The population whose blood samples were collected in the afternoon showed significantly higher values of BDNF compared to those of the morning shift. This same population presented lower BDNF levels when associated with ASD subtypes A1, A2, and A. We hypothesize that the lower values of BDNF measured in the morning shift were due to a response to the circadian cycle of cortisol, whose action inhibits the expression of serum neurotrophins.

Resumo Objetivo Verificar a associação entre os níveis de fator neurotrófico derivado do cérebro (brain-derived neurotrophic factor [BDNF]) e transtorno de estresse agudo (TEA) em pacientes que sofreram trauma físico. Métodos Os dados foram coletados em um hospital de emergência de Porto Alegre, Rio Grande do Sul, Brasil. Os participantes eram maiores de 18 anos, vítimas de trauma físico e estavam hospitalizados por um período mínimo de 48 horas. Um total de 117 pacientes hospitalizados que concordaram em participar da pesquisa foram agrupados de acordo com o turno de realização da coleta de sangue (38 sujeitos no turno da manhã e 79 sujeitos no turno da tarde), tiveram seus níveis de BDNF medidos e responderam a outros questionários. Os entrevistados também foram agrupados por idade em três faixas etárias: 18-30, 31-50 e 51-70 anos. Resultados Encontramos uma diferença significativa na distribuição de BDNF entre os turnos, sendo que o grupo da tarde apresentou níveis maiores de BDNF (U = 1906,5, p = 0,018). Houve diferença entre o grupo de 18-30 anos e o de 51-70 anos no turno da tarde (Umanhã = 1107, pmanhã = 0,575; Utarde = 7175, ptarde = 0,028). Conclusões A população cuja coleta ocorreu à tarde apresentou valores significativamente maiores de BDNF em relação à coleta do turno da manhã. Esta mesma população apresentou menores níveis dessa neurotrofina quando associada com os subtipos A1, A2 e A de TEA. É possível hipotetizar que os menores valores de BDNF aferidos na coleta do turno da manhã se devam a uma resposta ao ciclo circadiano do cortisol, cuja ação inibe a expressão de neurotrofinas séricas.

Humans , Male , Female , Adolescent , Adult , Aged , Young Adult , Wounds and Injuries/psychology , Brain-Derived Neurotrophic Factor/metabolism , Brazil , Hydrocortisone/metabolism , Biomarkers/metabolism , Surveys and Questionnaires , Circadian Rhythm , Stress Disorders, Traumatic, Acute/blood , Emergency Service, Hospital , Emergency Treatment/methods , Hospitalization , Middle Aged
Arch. latinoam. nutr ; 69(2): 99-106, jun. 2019. tab, graf
Article in Spanish | LILACS, LIVECS | ID: biblio-1053037


La obesidad infantil representa un factor importante en el desarrollo del síndrome metabólico (SM). En este sentido el factor neurotrófico derivado del cerebro (BDNF: Brain Derived Neurotrophic Factor) interviene en el metabolismo energético así como en vías que controlan el peso corporal y desórdenes metabólicos. El objetivo de este estudio fue determinar si hay una correlación entre el BDNF con los marcadores que definen al síndrome metabólico en una población infantil de México. Se integraron al estudio 100 niños con un rango de edad de 5-13 años, se estratificaron en tres grupos, normo peso, sobrepeso y obesidad, a los cuales se les determinaron las variables antropométricas, percentil de la tensión arterial sistólica y diastólica, concentraciones séricas de glucosa, triglicéridos, colesterol de alta densidad (HDL) y BDNF. Se aplicó ANOVA y una correlación de Pearson. Los resultados muestran que la prevalencia de SM utilizando los criterios de Cook y Weiss fue del 14%, mientras que por la Federación Internacional de Diabetes (IDF) es del 11%. La circunferencia de cintura, triglicéridos, colesterol HDL, presión arterial sistólica/diastólica y glucosa, mostraron diferencias significativas entre los grupos estudiados (*p<0,001). El BDNF se correlacionó positivamente con la desviación estándar del índice de masa corporal de acuerdo con la edad (DE-IMCE) (p=0,01), el percentil del perímetro de la cintura (p=0,00), la presión arterial sistólica (p=0,01) y las concentraciones plasmáticas de glucosa (p=0,02). Estos datos muestran que existe una correlación entre el BDNF con la DE-IMCE, la circunferencia de la cintura, la presión arterial sistólica y glucosa(AU)

Childhood obesity represents an important factor in the development of metabolic syndrome (MS). In this sense, the brain derived neurotrophic factor (BDNF) is involved in energy metabolism as well as in pathways that control body weight and metabolic disorders. The objective of this study was to determine if there is a correlation between BDNF with the markers that define the metabolic syndrome in a child population in Mexico. The study included 100 children with an age range of 5-13 years, stratified into three groups, normal weight, overweight and obesity, which were determined anthropometric variables, percentile of systolic and diastolic blood pressure, concentrations serum glucose, triglycerides, high density cholesterol (HDL) and BDNF. ANOVA and Pearson correlation were applied. The results show that the prevalence of MS using the Cook and Weiss criteria was 14%, while for the International Diabetes Federation (IDF) it is 11%. Waist circumference, triglycerides, HDL cholesterol, systolic/diastolic blood pressure and glucose showed significant differences between the groups studied (*p<0.001). The BDNF was positively correlated with the standard deviation of the body mass index according to age (DE-IMCE) (p=0.01), the percentile of the waist circumference (p=0.00), systolic blood pressure (p=0.01) and plasma glucose concentrations (p=0.02). These data show that there is a correlation between BDNF with DE-IMCE, waist circumference, systolic blood pressure and glucose(AU)

Humans , Male , Female , Child , Body Weights and Measures , Brain-Derived Neurotrophic Factor/analysis , Metabolic Syndrome/physiopathology , Lipid Metabolism , Insulin/metabolism , Anthropometry , Pediatric Obesity , Noncommunicable Diseases
Rev. Assoc. Med. Bras. (1992) ; 65(3): 361-369, Mar. 2019. tab, graf
Article in English | SES-SP, LILACS, SES-SP, SESSP-IDPCPROD, SES-SP | ID: biblio-1003035


SUMMARY BACKGROUND: There is no strong evidence on the link between inflammatory profile and pattern of drug treatment response in depressive patients that could result in Coronary Artery Disease occurrence. OBJECTIVE: This study aimed to compare the subclinical atherosclerosis markers, inflammatory profile, and BDNF production in Resistant Depression (RD) or Bipolar Affective Disorder (BAD) patients under conventional treatment. METHODS: The population evaluated was comprised of 34 RD, 43 BAD, and 41 controls. Subclinical atherosclerosis markers were evaluated using ultrasonography, tomography, and exercise stress test. Plasma concentrations of TNFα, IL-1β, IL-6, and BDNF were measured using Luminex100™. The usCRP concentration was measured using turbidimetric immunoassay. IL1B, IL6, and TNFA expression were determined using TaqMan®. For the statistical analysis, the significance level was established at p<0.05. RESULTS: Concerning subclinical atherosclerosis markers, only O2 consumption was reduced in the BAD group (p = 0.001). Although no differences were found in gene expression, BDNF and IL-1β plasma concentration was increased in the RD group (p = 0.002 and p = 0.005, respectively) even with an antidepressant treatment, which suggests that these drugs have no effect in IL-1β secretion and that the inflammasome may play a role in therapy response. CONCLUSION: Taken together, both BDNF and IL-1β plasma concentrations could be used to the early identification of RD patients.

RESUMO FUNDAMENTAÇÃO: Não há fortes evidências sobre a associação entre o perfil inflamatório e o padrão de resposta ao tratamento medicamentoso em pacientes depressivos que podem resultar em ocorrência de doença coronariana. OBJETIVO: O objetivo deste estudo foi comparar os marcadores de aterosclerose subclínica, o perfil inflamatório e a produção de BDNF em pacientes com Depressão Resistente (DR) ou Transtorno Afetivo Bipolar (BAD) sob tratamento convencional. MÉTODOS: A população avaliada incluiu 34 RD, 43 BAD e 41 controles. Os marcadores de aterosclerose subclínica foram avaliados por ultrassonografia, tomografia e teste de esforço. As concentrações plasmáticas de TNFα, IL-1β, IL-6 e BDNF foram medidas utilizando Luminex100TM. A concentração de usCRP foi medida por imunoensaio turbidimétrico. A expressão de IL1B, IL6 e TNFA foi determinada usando TaqMan®. Para as análises estatísticas, foi estabelecido o nível de significância de p < 0,05. RESULTADOS: Quanto aos marcadores de aterosclerose subclínica, apenas o consumo de O2 foi reduzido no grupo BAD (p = 0,001). Embora não tenham sido encontradas diferenças na expressão gênica, a concentração plasmática de BDNF e IL-1β foi aumentada no grupo RD (p = 0,002 e p = 0,005, respectivamente) mesmo sob tratamento antidepressivo, o que sugere que esses medicamentos não têm efeito na secreção de IL-1β e que o inflamassomo pode desempenhar um papel na resposta terapêutica. CONCLUSÃO: Juntas, as concentrações BDNF e IL-1β poderiam ser usadas para a identificação precoce de pacientes com DR.

Humans , Male , Female , Adult , Bipolar Disorder/blood , Brain-Derived Neurotrophic Factor/blood , Interleukin-1beta/blood , Depressive Disorder, Treatment-Resistant/blood , Reference Values , Bipolar Disorder/diagnosis , Bipolar Disorder/drug therapy , Biomarkers/blood , Body Mass Index , Logistic Models , Predictive Value of Tests , Interleukin-6/blood , Tumor Necrosis Factor-alpha/blood , Statistics, Nonparametric , Atherosclerosis/blood , Real-Time Polymerase Chain Reaction , Depressive Disorder, Treatment-Resistant/diagnosis , Depressive Disorder, Treatment-Resistant/drug therapy , Middle Aged , Anti-Inflammatory Agents/therapeutic use , Antidepressive Agents/therapeutic use
Rev. Col. Bras. Cir ; 46(2): e2094, 2019. tab, graf
Article in Portuguese | LILACS | ID: biblio-1003087


RESUMO Objetivo: determinar a expressão de neurotrofinas e seus receptores tirosina quinases em pacientes com osteossarcoma (OS) e sua correlação com desfechos clínicos. Métodos: biópsias de tumores primários de pacientes com OS tratados em uma única instituição, consecutivamente, entre 2002 e 2015, foram analisados através de imuno-histoquímica para expressão de receptores de tirosina quinase A e B (TrKA e TrKB), fator de crescimento neural (NGF) e fator neurotrófico derivado do cérebro (BDNF). De forma independente, dois patologistas classificaram os marcadores de imuno-histoquímica como negativos (negativos e focais fracos) ou positivos (moderado focal/difuso ou forte focal/difuso). Resultados: foram analisados dados de 19 pacientes (10 do sexo feminino e 9 do masculino) com mediana de idade de 12 anos (5 a 17,3 anos). Dos tumores, 83,3% estavam localizados em membros inferiores e 63,2% dos pacientes eram metastáticos ao diagnóstico. A sobrevida global em cinco anos foi de 55,3%. BDNF foi positivo em 16 pacientes (84%) e NGF em 14 pacientes (73%). TrKA e TrKB apresentaram coloração positiva em quatro (21,1%) e oito (42,1%) pacientes, respectivamente. A análise de sobrevida não demonstrou diferença significativa entre receptores TrK e neurotrofinas. Conclusão: amostras de OS primário expressam neurotrofinas e receptores TrK através de imuno-histoquímica. Estudos futuros podem auxiliar na identificação do papel das mesmas na patogênese do OS e determinar se há possível correlação prognóstica.

ABSTRACT Objective: to determine the expression of neurotrophins and their tyrosine-kinase receptors in patients with osteosarcoma (OS) and their correlation with clinical outcomes. Methods: we applied immunohistochemistry to biopsy specimens of patients consecutively treated for primary OS at a single institution between 2002 and 2015, analyzing them for expression receptors of tyrosine kinase A and B (TrKA and TrKB), neural growth factor (NGF) and brain derived neurotrophic factor (BDNF). Independently, two pathologists classified the immunohistochemical markers as negative (negative or weak focal) or positive (moderate focal/diffuse or strong focal/diffuse). Results: we analyzed data from 19 patients (10 females and 9 males), with median age of 12 years (5 to 17.3). Tumors' location were 83.3% in the lower limbs, and 63.2% of patients had metastases at diagnosis. Five-year overall survival was 55.3%. BDNF was positive in 16 patients (84%) and NGF in 14 (73%). TrKA and TrKB presented positive staining in four (21,1%) and eight (42,1%) patients, respectively. Survival analysis showed no significant difference between TrK receptors and neurotrophins. Conclusion: primary OS samples express neurotrophins and TrK receptors by immunohistochemistry. Future studies should explore their role in OS pathogenesis and determine their prognostic significance in larger cohorts.

Humans , Male , Female , Child, Preschool , Child , Adolescent , Bone Neoplasms/pathology , Osteosarcoma/pathology , Brain-Derived Neurotrophic Factor/analysis , Receptor, trkA/analysis , Receptor, trkB/analysis , Nerve Growth Factors/analysis , Reference Values , Bone Neoplasms/mortality , Immunohistochemistry , Biomarkers, Tumor , Osteosarcoma/mortality , Risk Factors , Statistics, Nonparametric , Kaplan-Meier Estimate
Article in Korean | WPRIM | ID: wpr-766566


Suicide is a complex phenomenon resulting from interactions between individual vulnerabilities and socio-environmental factors. The current review primarily focuses on research into the serotonin system, hypothalamic-pituitary-adrenal axis, neurotrophic factors, lipid metabolism, and functional neuroimaging studies. It has been found that dysfunctions in the serotonin system, hypothalamic-pituitary-adrenal axis abnormalities, and low brain-derived neurotrophic factor and cholesterol levels may be linked to suicide. Additionally, recent neuroimaging studies have suggested that structural and functional abnormalities in brain areas related to cognitive and emotional regulation may be associated with suicide. More research incorporating advanced methodological approaches may shed further light on the neurobiological basis of suicide.

Brain , Brain-Derived Neurotrophic Factor , Cholesterol , Functional Neuroimaging , Lipid Metabolism , Nerve Growth Factors , Neurobiology , Neuroimaging , Pituitary-Adrenal System , Serotonin , Suicide
Article in English | WPRIM | ID: wpr-765625


STUDY DESIGN: Animal study. OBJECTIVES: To investigate the effects of microelectric treatment by transcutaneous electrical nerve stimulation (TENS) on functional recovery and histological changes in a rat model of spinal cord injury (SCI). SUMMARY OF LITERATURE REVIEW: The effects of TENS on spasticity and its underlying mechanisms remain unclear. MATERIALS AND METHODS: SCI was induced by a 1.5-mm impactor with 200,000–260,000 dyne after laminectomy. Rats were divided into the following groups: group I (normal control), group II (microelectric treatment of 0 A), group III (microelectric treatment of 100 µA for 1 hr/day), group IV (microelectric treatment of 400 µA for 1 hr/day), and group V (microelectric treatment of 400 µA for 24 hr/day). After inducing SCI, rats were assessed by a sensory test with von Frey filaments and the locomotor recovery test (BBB rating scale) at 1, 4, 7, 14, 21, and 28 days. To evaluate spinal cord damage, histopathological studies were performed with hematoxylin and eosin. Brain-derived neurotrophic factor (BDNF) and TrkB immunohistochemistry studies were performed at 28 days. RESULTS: In groups IV and V, the BBB score had significantly improved on days 21 and 28 after SCI, and the TENS-treated groups showed significant neuronal recovery. After SCI, groups IV and V showed a significant recovery of locomotor function and the motor sensory response of the withdrawal threshold to 3.5 g. In addition, necrotic tissue and cystic spaces in the spinal cord were significantly reduced and BDNF/TrkB-positive cells were highly expressed in groups III, IV, and V. CONCLUSIONS: Microelectric treatment can play a role in facilitating the recovery of locomotion following SCI.

Animals , Brain-Derived Neurotrophic Factor , Eosine Yellowish-(YS) , Hematoxylin , Immunohistochemistry , Laminectomy , Locomotion , Models, Animal , Muscle Spasticity , Neurons , Rats , Spinal Cord Injuries , Spinal Cord , Transcutaneous Electric Nerve Stimulation
Article in Chinese | WPRIM | ID: wpr-775853


OBJECTIVE@#To explore the effect of electrical stimulation at auricular points (EAS) combined with sound masking on the expression of cAMP-response element binding protein (CREB), brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) in the auditory cortex of tinnitus rats.@*METHODS@#A total of 27 adult male SD rats were randomly divided into a control group, a model group and an EAS group. The rats in the model group and the EAS group were intervened with intraperitoneal injection of sodium salicylate to induce tinnitus model, while the rats in the control group were intervened with injection of 0.9% NaCl solution. After the model was successfully established, the rats in the EAS group were treated with electrical stimulation at "Shenmen" (TF) and "Yidan" (CO), combined with sound masking; the treatment was given once a day for 15 days. The gap prepulse inhibition of acoustic startle (GPIAS) and prepulse inhibition (PPI) testing were performed using the acoustic startle reflex starter package for rats. The expression of BDNF, TrkB, CREB and p-CREB in the auditory cortex of each group were measured with Western Blot analysis.@*RESULTS@#① Compared with the control group, the GPIAS values in 12 kHz, 16 kHz, 20 kHz and 28 kHz were significantly decreased in the model group (all 0.05).@*CONCLUSION@#EAS could improve the GPIAS values of high-frequency background sound in tinnitus rats, which may be related with the upregulation of the BDNF/TrkB/CREB signaling pathway in the auditory cortex, leading to the reversion of the maladaptive plasticity.

Acupuncture Points , Animals , Auditory Cortex , Brain-Derived Neurotrophic Factor , Metabolism , Cyclic AMP Response Element-Binding Protein , Metabolism , Electric Stimulation , Male , Rats , Rats, Sprague-Dawley , Receptor, trkB , Metabolism , Tinnitus , Metabolism , Therapeutics