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1.
Gene ; 806: 145920, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34455026

RESUMO

Depression is deemed a mood disorder characterized by a high rate of relapse. Therefore, overcoming of the recurrent depression is globally expecting. Kososan, a traditional Japanese herbal medicine, has been clinically used for mild depressive mood, and our previous studies have shown some evidence for its antidepressive-like efficacy in experimental animal models of depression. However, it remains unclear whether kososan has beneficial effects on recurrent depression. Here, we examined its effect using a mouse model of modified repeated social defeat stress (SDS) paradigm. Male BALB/c mice were exposed to a 5-min SDS from unfamiliar aggressive CD-1 mice for 5 days. Kososan extract (1.0 kg/kg/day) or an antidepressant milnacipran (60 mg/kg/day) was administered orally for 26 days (days 7-32) to depression-like mice with social avoidant behaviors on day 6. Single 5 min of SDS was subjected to mice recovered from the social avoidance on day 31, and then the recurrence of depression-like behaviors was evaluated on day 32. Hippocampal gene expression patterns were also assayed by DNA microarray analysis. Water- or milnacipran-administered mice resulted in a recurrence of depression-like behaviors by re-exposure of single SDS, whereas kososan-administered mice did not recur depression-like behaviors. Distinct gene expression patterns were also found for treating kososan and milnacipran. Collectively, this finding suggests that kososan exerts a preventive effect on recurrent depression-like behaviors in mice. Pretreatment of kososan is more useful for recurrent depression than that of milnacipran.


Assuntos
Antidepressivos/farmacologia , Depressão/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Proteínas do Tecido Nervoso/genética , Derrota Social , Estresse Psicológico/tratamento farmacológico , Administração Oral , Animais , Depressão/genética , Depressão/fisiopatologia , Depressão/psicologia , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Japão , Masculino , Medicina Kampo/métodos , Camundongos , Camundongos Endogâmicos BALB C , Milnaciprano/farmacologia , Anotação de Sequência Molecular , Proteínas do Tecido Nervoso/classificação , Proteínas do Tecido Nervoso/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Recidiva , Estresse Psicológico/genética , Estresse Psicológico/fisiopatologia
2.
Handb Exp Pharmacol ; 271: 379-400, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33712941

RESUMO

Temporal lobe epilepsy is considered to be one of the most common and severe forms of focal epilepsies. Patients frequently develop cognitive deficits and emotional blunting along progression of the disease. The high incidence of refractoriness to antiepileptic drugs and a frequent lack of admissibility to surgery pose an unmet medical challenge. In the urgent quest for novel treatment strategies, neuropeptides and their receptors are interesting candidates. However, their therapeutic potential has not yet been fully exploited. This chapter focuses on the functional role of the dynorphins (Dyns) and the kappa opioid receptor (KOR) system in temporal lobe epilepsy and the hippocampus.Genetic polymorphisms in the prepro-dynorphin (pDyn) gene causing lower levels of Dyns in humans and pDyn gene knockout in mice increase the risk to develop epilepsy. This suggests a role of Dyns and KOR as modulators of neuronal excitability. Indeed, KOR agonists induce inhibition of presynaptic neurotransmitter release, as well as postsynaptic hyperpolarization in glutamatergic neurons, both producing anticonvulsant effects.The development of new approaches to modulate the complex KOR signalling cascade (e.g. biased agonism and gene therapy) opens up new exciting therapeutic opportunities with regard to seizure control and epilepsy. Potential adverse side effects of KOR agonists may be minimized through functional selectivity or locally restricted treatment. Preclinical data suggest a high potential of such approaches to control seizures.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Animais , Dinorfinas , Epilepsia do Lobo Temporal/tratamento farmacológico , Hipocampo , Humanos , Camundongos , Receptores Opioides kappa
3.
Behav Brain Res ; 417: 113630, 2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-34656691

RESUMO

Social isolation gained discussion momentum due to the COVID-19 pandemic. Whereas many studies address the effects of long-term social isolation in post-weaning and adolescence and for periods ranging from 4 to 12 weeks, little is known about the repercussions of adult long-term social isolation in middle age. Thus, our aim was to investigate how long-term social isolation can influence metabolic, behavioural, and central nervous system-related areas in middle-aged mice. Adult male C57Bl/6 mice (4 months-old) were randomly divided into Social (2 cages, n = 5/cage) and Isolated (10 cages, n = 1/cage) housing groups, totalizing 30 weeks of social isolation, which ended concomitantly with the onset of middle age of mice. At the end of the trial, metabolic parameters, short-term memory, anxiety-like behaviour, and physical activity were assessed. Immunohistochemistry in the hippocampus (ΔFosB, BDNF, and 8OHDG) and hypothalamus (ΔFosB) was also performed. The Isolated group showed impaired memory along with a decrease in hippocampal ΔFosB at dentate gyrus and in BDNF at CA3. Food intake was also affected, but the direction depended on how it was measured in the Social group (individually or in the group) with no alteration in ΔFosB at the hypothalamus. Physical activity parameters increased with chronic isolation, but in the light cycle (inactive phase), with some evidence of anxiety-like behaviour. Future studies should better explore the timepoint at which the alterations found begin. In conclusion, long-term social isolation in adult mice contributes to alterations in feeding, physical activity pattern, and anxiety-like behaviour. Moreover, short-term memory deficit was associated with lower levels of hippocampal ΔFosB and BDNF in middle age.


Assuntos
Ansiedade/etiologia , COVID-19 , Comportamento Alimentar , Hipocampo/metabolismo , Locomoção , Transtornos da Memória/etiologia , Isolamento Social , Fatores Etários , Animais , Comportamento Animal/fisiologia , Fator Neurotrófico Derivado do Encéfalo , COVID-19/prevenção & controle , Modelos Animais de Doenças , Comportamento Alimentar/fisiologia , Abrigo para Animais , Hipotálamo/metabolismo , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-fos/metabolismo
4.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(11): 961-966, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34809734

RESUMO

Objective To investigate the cognitive differences between male and female mice with sepsis-associated encephalopathy (SAE) and its underlying mechanism. Methods The SAE model was induced by caecal ligation and puncture (CLP) in male and female mice aged from 6 to 8 weeks. The cognitive functions of the mice were evaluated by novel object recognition test and contextual fear conditioning test. The expression and distribution of α7 nicotinic acetylcholinergic receptor (α7nAChR) and the proportion of M2 microglia in hippocampus of SAE mice were detected by immunofluorescence staining, and the level of α7nAChR protein was detected by Western blot. Results The cognitive function of male SAE mice was significantly impaired, and the expression level of α7nAChR protein in hippocampus of male SAE mice decreased significantly compared with that of female SAE mice. At the same time, the proportion of M2 microglia in SAE male mice was significantly lower than that in female mice. Conclusion The expression level of α7nAChR protein in hippocampus of SAE male mice is significantly lower than that of SAE female mice, and the proportion of M2 microglia is relatively lower, which lead to the cognitive dysfunction of SAE male mice.


Assuntos
Disfunção Cognitiva , Encefalopatia Associada a Sepse , Animais , Feminino , Hipocampo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia , Encefalopatia Associada a Sepse/genética , Receptor Nicotínico de Acetilcolina alfa7/genética
5.
Alzheimers Res Ther ; 13(1): 184, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34749800

RESUMO

BACKGROUND: The cannabinoid CB2 receptor (CB2R), which is a target to afford neuroprotection, and N-methyl-D-aspartate (NMDA) ionotropic glutamate receptors, which are key in mediating excitatory neurotransmission, are expressed in both neurons and glia. As NMDA receptors are the target of current medication in Alzheimer's disease patients and with the aim of finding neuromodulators of their actions that could provide benefits in dementia, we hypothesized that cannabinoids could modulate NMDA function. METHODS: Immunocytochemistry was used to analyze the colocalization between CB2 and NMDA receptors; bioluminescence resonance energy transfer was used to detect CB2-NMDA receptor complexes. Calcium and cAMP determination, mitogen-activated protein kinase (MAPK) pathway activation, and label-free assays were performed to characterize signaling in homologous and heterologous systems. Proximity ligation assays were used to quantify CB2-NMDA heteromer expression in mouse primary cultures and in the brain of APPSw/Ind transgenic mice, an Alzheimer's disease model expressing the Indiana and Swedish mutated version of the human amyloid precursor protein (APP). RESULTS: In a heterologous system, we identified CB2-NMDA complexes with a particular heteromer print consisting of impairment by cannabinoids of NMDA receptor function. The print was detected in activated primary microglia treated with lipopolysaccharide and interferon-γ. CB2R activation blunted NMDA receptor-mediated signaling in primary hippocampal neurons from APPSw/Ind mice. Furthermore, imaging studies showed that in brain slices and in primary cells (microglia or neurons) from APPSw/Ind mice, there was a marked overexpression of macromolecular CB2-NMDA receptor complexes thus becoming a tool to modulate excessive glutamate input by cannabinoids. CONCLUSIONS: The results indicate a negative cross-talk in CB2-NMDA complexes signaling. The expression of the CB2-NMDA receptor heteromers increases in both microglia and neurons from the APPSw/Ind transgenic mice, compared with levels in samples from age-matched control mice.


Assuntos
Canabinoides , Microglia , Receptores de Canabinoides , Receptores de N-Metil-D-Aspartato , Animais , Hipocampo/metabolismo , Humanos , Camundongos , Microglia/metabolismo , N-Metilaspartato , Neurônios/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
7.
Neurologia (Engl Ed) ; 36(9): 673-680, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34752345

RESUMO

INTRODUCTION: Chronic exposure to low doses of ozone causes oxidative stress and loss of regulation of the inflammatory response, leading to progressive neurodegeneration. OBJECTIVE: We studied the effect of chronic exposure to low doses of ozone on IL-17A concentration and expression in neurons, microglia, astrocytes, and T cells in the rat hippocampus. METHODS: We used 72 Wistar rats, divided into 6 groups (n=12): a control group (no ozone exposure) and 5 groups exposed to ozone (0.25ppm, 4h daily) for 7, 15, 30, 60, and 90 days. We processed 6 rats from each group to quantify IL-17A by ELISA; the remaining 6 were processed for immunohistochemistry (against IL-17A and GFAP, Iba1, NeuN, and CD3). RESULTS: The ELISA study data showed a significant increase in IL-17A concentrations in the 7-, 15-, 30-, and 60-day exposure groups, with regard to the control group (P<.05). Furthermore, they indicate that hippocampal neurons were the cells showing greatest immunoreactivity against IL-17A between 60 and 90 days of exposure to ozone; we also observed an increase in activated astrocytes in the 30- and 60-day exposure groups. CONCLUSION: Exposure to ozone in rats induces an increase in IL-17A expression, mainly in hippocampal neurons, accompanied by hippocampal astrocyte activation during chronic neurodegeneration, similar to that observed in Alzheimer disease in humans.


Assuntos
Hipocampo , Interleucina-17 , Ozônio , Animais , Hipocampo/metabolismo , Interleucina-17/metabolismo , Microglia/metabolismo , Ozônio/efeitos adversos , Ratos , Ratos Wistar
8.
Georgian Med News ; (319): 165-170, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34749344

RESUMO

The study included adolescents (P30-36), adult (P125-130) and aged (P330-340) male Wistar rats - 4 animals in each age group. The rats were housed individually, in wire-top polypropylene cages (30-cm width x 30 cm length x 25 cm height) and maintained on a 12-h light/dark cycle. Standard food pellets and tap water were ad libitum. The animal maintenance and electron microscopic procedures were conducted in accordance with European Union Directive on the protection of animals used for scientific research. The Ultrastructure of adult and adolescent rats are almost same. However, remarkable changes are expressed between adult and senescent rats. Precisely, in the last one there are following ultrastructural modifications - lipofuscin concentrations, small destructive cytoplasmic organelles, changes in presynaptic vesicular and mitochondrial quantity. Rare apoptotic signs in neurons. Analysis of all this means that aging in rat's hippocampus causes selective changes, also it underlines changes in neurotransmission and neuronal developmental pathways.


Assuntos
Elétrons , Hipocampo , Animais , Masculino , Microscopia Eletrônica , Neurônios , Ratos , Ratos Wistar
9.
Zhongguo Zhong Yao Za Zhi ; 46(19): 5044-5051, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738400

RESUMO

Chronic unpredicted mild stress(CUMS) combined with isolated feeding was used to induce depressed rat model. The anti-depressant effects of Zhizichi Decoction(ZZCD) and its solid fermented product(ZZC) were analyzed by behavioral test and comparison of pathological tissues of hippocampus and liver, metabolic characteristics of intestinal flora, and relative abundance of species. The results showed that ZZC could increase sucrose preference, shorten the immobility time in the forced swim test and tail suspension test(P<0.05), and repair damaged hippocampus and liver tissues, and the effect was superior to that of ZZCD. The results of Biolog ECO plates showed that the average well color development(AWCD) of intestinal flora in the model group significantly decreased and the metabolic levels of sugar and amino acids were reduced, while the AWCD of the treatment groups increased. The metabolic levels of the two carbon sources were improved in the ZZC group, while only sugar metabolic level was elevated in the ZZCD group. Metagenomic analysis of intestinal flora showed that the ratio of Firmicutes/Bacteroidetes was 3.87 in the control group, 21.77 in the model group, 5.91 in the ZZC group, and 18.48 in the ZZCD group. Lactobacillus increased by 3.28 times, and Prevotella and Bacteroidetes decreased by 75.59% and 76.39%, respectively in the model group as compared with that in the control group. Lactobacillus decreased by 31.13%, and Prevotella and Bacteroidetes increased by more than three times in the ZZC group as compared with that in the model group, while the corresponding changes in the ZZCD group were not significant. ZZC could improve depression-like beha-viors by regulating the structure of intestinal flora and metabolic functions and repairing damaged hippocampus and liver tissues in depressed rats, showing an anti-depressant effect superior to that of ZZCD. This study is expected to provide a basis for the development of new anti-depressant food products.


Assuntos
Microbioma Gastrointestinal , Hipocampo , Animais , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Fermentação , Ratos , Estresse Psicológico
10.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(6): 638-643, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34821098

RESUMO

Objective: To investigate the effects of Moringa leaves on the cognitive dysfunction and apoptosis of hippocampal neurons in diabetic rats induced by streptozotocin (STZ). Methods: Fifty male SD rats were selected, and 10 rats were randomly selected as the control group. The other 40 rats were treated with STZ at the dose of 25 mg/kg by intraperitoneal injection. The 40 diabetic rats were randomly divided into model group, Moringa oleifera low-dose, medium-dose and high-dose group. The rats in Moringa oleifera groups were treated with Moringa oleifera at the doses of 2.0, 4.0 and 8.0 g/kg by gavage, the control group and model group were treated with the same amount of normal saline once a day, for 8 weeks. Morris water maze test was used to evaluate the learning and memory ability of rats. Pathological changes of hippocampal neurons and expressions of Bax, caspase-3 and bcl-2 protein in each group were observed by the sections were stained with HE staining and immunohistochemistry. Enzyme linked immunosorbent assay (ELISA) was used to detect tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in rat. Results: compared with the control group, the blood glucose of the model group was increased significantly (P<0.01), and the blood insulin level was decreased significantly (P<0.05); compared with the model group, the blood glucose values of Moringa oleifera groups were decreased significantly (P<0.05, P<0.01), and the blood insulin levels of middle and high dose Moringa oleifera group were increased significantly (P<0.05, P<0.01). There was no significant difference in FBG and INS among the three groups (P>0.05). In Morris water maze test, compared with the model group, the latency of Moringa oleifera groups was significantly shorter (P<0.05); the residence time in target quadrant of Moringa oleifera groups with different doses was significantly prolonged (P<0.05). Compared with the model group, the contents of TNF - α, IL-6 and protein expression in low, medium and high dose groups of Moringa oleifera were decreased significantly (P<0.05). HE staining and immunohistochemical staining results showed that Moringa oleifera medium dose group was positive, brown yellow, fine granular, compared with the model group. The number of neuronal apoptosis was significantly reduced in the middle dose group (53.21±7.19,P<0.01); the protein expressions of Bax, caspase-3 and the ratio of Bax/Bcl-2 in hippocampus were significantly decreased in the middle dose group (P<0.05). Conclusion: The mechanisms of Moringa leaves on the cognitive dysfunction and apoptosis of hippocampal neurons may be related to regulating the protein expressions of Bax, Bcl-2 and Caspase-3, reducing the contents of inflammatory factors TNF-α and IL-6.


Assuntos
Diabetes Mellitus Experimental , Animais , Apoptose , Cognição , Diabetes Mellitus Experimental/tratamento farmacológico , Hipocampo , Neurônios , Folhas de Planta , Ratos , Ratos Sprague-Dawley
11.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(6): 665-672, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34821103

RESUMO

Objective: To investigate the effects of aerobic exercise plus spirulina polysaccharide(SP) supplement on the related protein expressions of p75NTR signal in hippocampal and the improvement of learning and memory of type 2 diabetes rats. Methods: The model of type 2 diabetic rats was established by fed high-fat diet for four weeks together with intraperitoneal injecting a low dose of STZ. The model rats were randomly divided into diabetic model group(B),diabetic exercise group(C),diabetic+SP group(D)and diabetic exercise+SP group(E), another normal control group(A)without any intervention was set up,12 rats in each group. The rats in Group C and E were treated with intervention of swimming training for six weeks. The rats in Group D and E were treated with SP intragastrically for 6 weeks. Learning and memory abilities were observed by Morris water maze test. The hippocampus cell apoptosis was observed by Tunnel staining, and BDNF content and the expressions of p75NTR, cleaved caspase-3 of hippocampus were tested by ELISA, Western blot and immunohistochemistry, respectively. At the same time, the changes of blood glucose and levels of serum insulin were examined. Results: ①Compared with Group A at different time points, the body weight of Group B was decreased significantly(P<0.01). Compared with Group B at different time points, the body weight of Group C,D and E had no difference (P>0.05). Compared with Group A, levels of the blood glucose and serum insulin Group B were increased significantly(P<0.01).Compared with Group B, the levels in the intervention groups were decreased significantly (P<0.01); ②Compared with Group A, the escape latencies of Group B were prolonged significantly(P<0.01), platform quadrant residence duration and the times of crossing platform were decreased (P<0.01). Compared with Group B, the escape latencies of the intervention groups were shortened (P<0.05 or P<0.01), and the times of crossing platform were increased (P<0.05 or P<0.01). ③Compared with Group B, the neural cells apoptosis of the intervention rats was decreased, and the protein expressions of p75NTR and cleaved caspase-3 were decreased (P<0.05 or P<0.01), however the expression of BDNF was increased significantly (P<0.05 or P<0.01). Conclusion: Aerobic exercise and SP supplement can improve the learning-memory ability of type 2 diabetes rats, and the improvement effect of exercise combined with SP is markedly better than that of exercise and SP alone, the mechanism might be related to better regulating p75NTR signal related protein expressions and then inhibiting apoptosis in hippocampus of rats with type 2 diabetes.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Spirulina , Animais , Diabetes Mellitus Experimental/terapia , Hipocampo , Polissacarídeos , Ratos , Ratos Sprague-Dawley , Natação
12.
Transl Psychiatry ; 11(1): 497, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34602607

RESUMO

Cognitive deficits commonly accompany psychiatric disorders but are often underrecognised, and difficult to treat. The 5-HT4 receptor is a promising potential treatment target for cognitive impairment because in animal studies 5-HT4 receptor agonists enhance hippocampal-dependent memory processes. To date, there has been little work translating these effects to humans. We tested whether short-term administration of the 5-HT4 partial agonist, prucalopride, modified behavioural and neural (fMRI) memory processing in 44 healthy human volunteers using an experimental medicine model. We found that participants who had received six days of prucalopride treatment were significantly better at recalling previously seen neutral images and distinguishing them from new images. At a neural level, prucalopride bilaterally increased hippocampal activity and activity in the right angular gyrus compared with placebo. Taken together, these findings demonstrate the potential of 5-HT4-receptor activation for cognitive enhancement in humans, and support the potential of this receptor as a treatment target for cognitive impairment.


Assuntos
Agonistas do Receptor 5-HT4 de Serotonina , Serotonina , Benzofuranos , Hipocampo/metabolismo , Humanos , Receptores 5-HT4 de Serotonina/metabolismo , Agonistas do Receptor 5-HT4 de Serotonina/farmacologia
13.
Zhonghua Yi Xue Za Zhi ; 101(37): 3024-3028, 2021 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-34638195

RESUMO

Objective: To compare the hippocampal volume and local surface morphology changes in patients with mesial temporal lobe (mTLE) using the voxel-based morphometry and spherical harmonic methods respectively. Methods: A total of 66 patients (31 males and 35 females, age range from 17 to 48 (28±8) years) with mTLE and 80 age-and gender-matched controls (38 males and 42 females, age range from 19 to 46 (27±7) years) were retrospectively collected from July 2009 to February 2019 at Jinling hospital.. High resolution structural MRI of the whole brain, three-dimensional T1-weighted data(3DT1) were acquired from each subject. The changes of hippocampal volume and surface morphology were evaluated between mTLE groups and controls for observing the hippocampal atrophy pattern by using voxel-based morphometry and spherical harmonic shape descriptions point distribution model respectively. Pearson correlation analysis was conducted for observing the relationship between the morphological changes of hippocampus and disease duration. Results: Compared with the controls, hippocampal volume on the affected side in patients with mTLE was significantly reduced (Z-score:-1.55±0.57 vs 0.38±0.58, P<0.001) and negatively correlated with disease duration (r=-0.297, P=0.016). Furthermore, surface morphology analysis subtly showed that the atrophy of the affected hippocampus in patients with mTLE mainly located in the head, mesial lateral part and posterior tail of the hippocampus. Their displacement values were negatively correlated with disease duration (r=-0.336, P=0.006) and positively associated with the hippocampal grey matter volume (r=0.336, P=0.006). Conclusions: Voxel-based morphometry analysis reveals a global reduction in hippocampal volume, while the morphological measurement method based on surface shape can describe the local morphological changes of hippocampal atrophy.


Assuntos
Epilepsia do Lobo Temporal , Adolescente , Adulto , Epilepsia do Lobo Temporal/diagnóstico por imagem , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Lobo Temporal/diagnóstico por imagem , Adulto Jovem
14.
Nat Commun ; 12(1): 5740, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593806

RESUMO

NG2 glia, also known as oligodendrocyte precursor cells (OPCs), play an important role in proliferation and give rise to myelinating oligodendrocytes during early brain development. In contrast to other glial cell types, the most intriguing aspect of NG2 glia is their ability to directly sense synaptic inputs from neurons. However, whether this synaptic interaction is bidirectional or unidirectional, or its physiological relevance has not yet been clarified. Here, we report that NG2 glia form synaptic complexes with hippocampal interneurons and that selective photostimulation of NG2 glia (expressing channelrhodopsin-2) functionally drives GABA release and enhances inhibitory synaptic transmission onto proximal interneurons in a microcircuit. The mechanism involves GAD67 biosynthesis and VAMP-2 containing vesicular exocytosis. Further, behavioral assays demonstrate that NG2 glia photoactivation triggers anxiety-like behavior in vivo and contributes to chronic social defeat stress.


Assuntos
Ansiedade/psicologia , Hipocampo/patologia , Células Precursoras de Oligodendrócitos/metabolismo , Estresse Psicológico/complicações , Ácido gama-Aminobutírico/metabolismo , Animais , Ansiedade/etiologia , Ansiedade/patologia , Diferenciação Celular , Modelos Animais de Doenças , Exocitose , Glutamato Descarboxilase/biossíntese , Hipocampo/citologia , Humanos , Interneurônios/patologia , Masculino , Camundongos , Camundongos Transgênicos , Técnicas de Patch-Clamp , Derrota Social , Estresse Psicológico/patologia , Estresse Psicológico/psicologia , Sinapses/patologia , Transmissão Sináptica/fisiologia , Proteína 2 Associada à Membrana da Vesícula/metabolismo
15.
Transl Psychiatry ; 11(1): 516, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625534

RESUMO

Electroconvulsive therapy (ECT) is of the most effective treatments available for treatment-resistant depression, yet it is underutilized in part due to its reputation of causing cognitive side effects in a significant number of patients. Despite intensive neuroimaging research on ECT in the past two decades, the underlying neurobiological correlates of cognitive side effects remain elusive. Because the primary ECT-related cognitive deficit is memory impairment, it has been suggested that the hippocampus may play a crucial role. In the current study, we investigated 29 subjects with longitudinal MRI and detailed neuropsychological testing in two independent cohorts (N = 15/14) to test if volume changes were associated with cognitive side effects. The two cohorts underwent somewhat different ECT study protocols reflected in electrode placements and the number of treatments. We used longitudinal freesurfer algorithms (6.0) to obtain a bias-free estimate of volume changes in the hippocampus and tested its relationship with neurocognitive score changes. As an exploratory analysis and to evaluate how specific the effects were to the hippocampus, we also calculated this relationship in 41 other areas. In addition, we also analyzed cognitive data from a group of healthy volunteers (N = 29) to assess practice effects. Our results supported the hypothesis that hippocampus enlargement was associated with worse cognitive outcomes, and this result was generalizable across two independent cohorts with different diagnoses, different electrode placements, and a different number of ECT sessions. We found, in both cohorts, that treatment robustly increased the volume size of the hippocampus (Cohort 1: t = 5.07, Cohort 2: t = 4.82; p < 0.001), and the volume increase correlated with the neurocognitive T-score change. (Cohort 1: r = -0.68, p = 0.005; Cohort 2: r = -0.58; p = 0.04). Overall, our research indicates that novel treatment methods serving to avoid hippocampal volume increase may result in a better side effect profile.


Assuntos
Transtornos Cognitivos , Eletroconvulsoterapia , Cognição , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética
16.
Phys Rev Lett ; 127(14): 148101, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34652209

RESUMO

Biological neuronal networks excel over artificial ones in many ways, but the origin of this is still unknown. Our symbolic dynamics-based tool of excess entropies suggests that neuronal cultures naturally implement data structures of a higher level than what we expect from artificial neural networks, or from close-to-biology neural networks. This points to a new pathway for improving artificial neural networks towards a level demonstrated by biology.


Assuntos
Modelos Neurológicos , Neurônios/fisiologia , Entropia , Hipocampo/fisiologia , Humanos
17.
Neuron ; 109(19): 3071-3074, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34619087

RESUMO

Hippocampal sharp-wave ripples (SWRs) have been proposed to support memory-based decision-making. A new study by Gillespie et al. (in this issue of Neuron) provides important new insights on how past experiences and future choices are reflected in neuronal activity during SWRs.


Assuntos
Hipocampo , Neurônios , Cognição
18.
J Agric Food Chem ; 69(41): 12333-12343, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34633809

RESUMO

Memory impairment is becoming a potential health issue with the delicacy of diet and social stress. Sea cucumber peptides (SCP) prevent memory impairment, as previously reported. In this study, further research was performed using hippocampal lysine-acetylome to explore molecular regulation mechanisms. C57BL/6 mice were treated with scopolamine via intraperitoneal injection to simulate memory impairment. To determine the influence of SCP on the total acetylated-protein level of the hippocampus, acetylated-proteomics was performed. SCP increased the acetylation level of histone (H3 and H4). Meanwhile, for non-histones, the differentially acetylated proteins were involved in multiple memory-related pathways, as shown by KEGG enrichment analysis. Additionally, long-term potentiation was confirmed by western blotting. Finally, a combined analysis of proteome and lysine acetylome revealed that SCP contributed to synaptic vesicle cycle regulation and dopamine metabolism. Consequently, our findings revealed that SCP was potentially neuroprotective by regulating post-transcriptional hippocampal protein acetylation.


Assuntos
Lisina , Pepinos-do-Mar , Acetilação , Animais , Hipocampo/metabolismo , Lisina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Peptídeos , Processamento de Proteína Pós-Traducional , Proteoma/genética , Proteoma/metabolismo , Pepinos-do-Mar/metabolismo
19.
Zhen Ci Yan Jiu ; 46(10): 851-6, 2021 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-34698459

RESUMO

OBJECTIVE: To explore the mechanism of acupuncture in improving cognitive ability by regulating hippocampal phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway in vascular dementia (VD) rats. METHODS: A total of 80 male SD rats were randomized into sham operation, model, non-acupoint and acupoint groups (n=18 per group). The VD model was established by ligation of the bilateral common carotid arteries. For rats of the acupoint group, "Baihui" (GV20) and bilateral "Zusanli "(ST36) were needled and stimulated by twirling the needles with reinforcing method, and for rats of the non-acupoint group, the bilateral subcostal spots (about 10 mm superior to the iliac cresta) were needled and stimulated by twirling the needles with uniform reinforcing and reducing method. The treatment was conducted once daily, 6 times a week for two weeks, beginning 3 days after successful modeling. Rats of the sham operation group and model group received grasps as those in the acupoint groups. Morris water maze test was used to detect the abilities of learning and spatial memory. The contents of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and the activities of acetylcholinesterase (AChE) and acetylcholine transferase (ChAT) in the hippocampus tissue were detected by using ELISA, changes of hippocampal mitochondrial membrane potential (MMP) detected using JC-1 fluorescence probe, and the expression levels of hippocampal phosphorylated (p)-PI3K, p-Akt and mTOR proteins measured using Western blot. RESULTS: Compared with the sham operation group, the escape latency, contents of ROS and MDA, and AChE activity were significantly increased (P<0.05), and the spatial memory ability, SOD activity, ChAT activity, MMP, p-PI3K, p-Akt and mTOR expression levels were significantly decreased in the model group (P<0.05). Compared with the model group, carotid artery ligature-induced increase of the escape latency, contents of ROS and MDA, and AChE activity, and decrease of the spatial memory ability, SOD activity, ChAT activity, MMP, p-PI3K, p-Akt and mTOR expression levels were significantly reversed in the acupuncture group (P< 0.05), but not in the non-acupoint group (P>0.05). The therapeutic effects of acupoint needling were obviously superior to those of non-acupoint needling in decreasing the escape latency, contents of ROS and MDA, and AChE activity (P<0.05), and in increasing the spatial memory ability, SOD activity, ChAT activity, MMP, p-PI3K, p-Akt and mTOR expre-ssion levels (P<0.05). CONCLUSION: Acupuncture can improve cognitive function of VD rats, which may be related with its functions in easing oxidative stress and MMP reduction by activating PI3K/Akt/mTOR signaling pathway in the hippocampus.


Assuntos
Terapia por Acupuntura , Demência Vascular , Acetilcolinesterase , Animais , Cognição , Demência Vascular/genética , Demência Vascular/terapia , Hipocampo , Masculino , Fosfatidilinositol 3-Quinase , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Sprague-Dawley , Serina-Treonina Quinases TOR/genética
20.
ACS Chem Neurosci ; 12(20): 3939-3946, 2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-34601865

RESUMO

Major depressive disorder has become an increasingly serious disease in the world. However, convenient antidepressants have low efficacy and slow onset defects, which is dangerous for suicidal tendency patients. Nowadays, rapid antidepressant research has become the focus. Merazin hydrate (MH), a component of the natural herb Fructus Aurantii, has been shown to produce rapid antidepressant-like effects in animal models. However, the mechanism of its rapid antidepressant-like effects was still elusive like that of ketamine. The study aimed to reveal the relationship between the rapid antidepressant-like effects of MH and mTOR signaling, which is closely related to rapid antidepressants. The results showed that a single administration of MH was capable of reversing the behavioral defects at 2 h in two classic depressive models including learned helplessness (LH) and chronic mild stress (CMS). Moreover, the phosphorylated expression of mTOR, reduced by LH or CMS, was upregulated after a single administration of MH, and the expressions of BDNF and synaptic proteins in the hippocampus were also reversed 2 h later, similar to ketamine. Moreover, LH increased the expressions of eNOS, IL-10, and TNF-α in serum, which were all reversed by a single dose of MH at 2 h, similar to ketamine. Furthermore, we used rapamycin, an antagonist of mTOR, to confirm whether the rapid antidepressant-like effects of MH depend on mTOR or not. We found that inhibiting the activation of mTOR blocked the rapid antidepressant-like effects of MH, which also inhibited the upregulation of expressions of BDNF and PSD95. To sum up, the rapid antidepressant effect of MH depended on the activation of mTOR to regulate downstream BNDF and synaptic protein expressions.


Assuntos
Transtorno Depressivo Maior , Animais , Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/tratamento farmacológico , Hipocampo/metabolismo , Humanos , Serina-Treonina Quinases TOR/metabolismo
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