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1.
Cereb Cortex ; 29(4): 1509-1519, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29522177

RESUMO

ß-Catenin has been implicated in major depressive disorder (MDD), which is associated with synaptic plasticity and dendritic arborization. MicroRNAs (miRNA) are small noncoding RNAs containing about 22 nucleotides and involved in a variety of physiological and pathophysiological process, but their roles in MDD remain largely unknown. Here, we investigated the expression and function of miRNAs in the mouse model of chronic social defeat stress (CSDS). The regulation of ß-catenin by selected miRNA was validated by silico prediction, target gene luciferase reporter assay, and transfection experiment in neurons. We demonstrated that the levels of miR-214-3p, which targets ß-catenin transcripts were significantly increased in the medial prefrontal cortex (mPFC) of CSDS mice. Antagomir-214-3p, a neutralizing inhibitor of miR-214-3p, increased the levels of ß-catenin and reversed the depressive-like behavior in CSDS mice. Meanwhile, antagomir-214-3p increased the amplitude of miniature excitatory postsynaptic current (mEPSC) and the number of dendritic spines in mPFC of CSDS mice, which may be related to the elevated expression of cldn1. Furthermore, intranasal administered antagomir-214-3p also significantly increased the level of ß-catenin and reversed the depressive-like behaviors in CSDS mice. These results may represent a new therapeutic target for MDD.


Assuntos
Depressão/fisiopatologia , MicroRNAs/fisiologia , Estresse Psicológico/fisiopatologia , beta Catenina/fisiologia , Administração Intranasal , Animais , Antagomirs/administração & dosagem , Claudina-1/genética , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/fisiologia , Depressão/etiologia , Depressão/genética , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Regulação da Expressão Gênica , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiopatologia , Estresse Psicológico/genética , beta Catenina/genética
2.
Int J Neuropsychopharmacol ; 18(6)2014 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-25522427

RESUMO

BACKGROUND: SKF83959 stimulates the phospholipase Cß/inositol phosphate 3 pathway, resulting in the activation of Ca(2+)/calmodulin-dependent kinase IIα, which affects the synthesis of brain-derived neurotrophic factor, a neurotrophic factor critical for the pathophysiology of depression. Previous reports showed that SKF83959 elicited antidepressant activity in the forced swim test and tail suspension test as a novel triple reuptake inhibitor. However, there are no studies showing the effects of SKF83959 in a chronic stress model of depression and the role of phospholipase C/inositol phosphate 3/calmodulin-dependent kinase IIα/brain-derived neurotrophic factor pathway in SKF83959-mediated antidepressant effects. METHODS: In this study, SKF83959 was firstly investigated in the chronic social defeat stress model of depression. The changes in hippocampal neurogenesis, dendrite spine density, and brain-derived neurotrophic factor signaling pathway after chronic social defeat stress and SKF83959 treatment were then investigated. Pharmacological inhibitors and small interfering RNA/short hairpin RNA methods were further used to explore the antidepressive mechanisms of SKF83959. RESULTS: We found that SKF83959 produced antidepressant effects in the chronic social defeat stress model and also restored the chronic social defeat stress-induced decrease in hippocampal brain-derived neurotrophic factor signaling pathway, dendritic spine density, and neurogenesis. By using various inhibitors and siRNA/shRNA methods, we further demonstrated that the hippocampal dopamine D5 receptor, phospholipase C/inositol phosphate 3/ calmodulin-dependent kinase IIα pathway, and brain-derived neurotrophic factor system are all necessary for the SKF83959 effects. CONCLUSION: These results suggest that SKF83959 can be developed as a novel antidepressant and produces antidepressant effects via the hippocampal D5/ phospholipase C/inositol phosphate 3/calmodulin-dependent kinase IIα/brain-derived neurotrophic factor pathway.


Assuntos
2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/análogos & derivados , Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Glicoproteínas de Membrana/efeitos dos fármacos , Proteínas Tirosina Quinases/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Comportamento Social , Estresse Psicológico/tratamento farmacológico , 2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/farmacologia , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Doença Crônica , Depressão/metabolismo , Depressão/fisiopatologia , Depressão/psicologia , Modelos Animais de Doenças , Agonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Ativação Enzimática , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Inositol 1,4,5-Trifosfato/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Tirosina Quinases/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptores de Dopamina D5/agonistas , Receptores de Dopamina D5/genética , Receptores de Dopamina D5/metabolismo , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Fosfolipases Tipo C/metabolismo
3.
Am J Physiol Cell Physiol ; 303(4): C376-84, 2012 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-22592406

RESUMO

Acid-sensing ion channels (ASICs) have been reported to play a role in the neuronal dopamine pathway, but the exact role in neurotransmitter release remains elusive. Human neuroblastoma SH-SY5Y is a dopaminergic neuronal cell line, which can release monoamine neurotransmitters. In this study, the expression of ASICs was identified in SH-SY5Y cells to further explore the role of ASICs in vesicular release stimulated by acid. We gathered evidence that ASICs could be detected in SH-SY5Y cells. In whole cell patch-clamp recording, a rapid decrease in extracellular pH evoked inward currents, which were reversibly inhibited by 100 µM amiloride. The currents were pH dependent, with a pH of half-maximal activation (pH(0.5)) of 6.01 ± 0.04. Furthermore, in calcium imaging and FM 1-43 dye labeling, it was shown that extracellular protons increased intracellular calcium levels and vesicular release in SH-SY5Y cells, which was attenuated by PcTx1 and amiloride. Interestingly, N-type calcium channel blockers inhibited the vesicular release induced by acidification. In conclusion, ASICs are functionally expressed in SH-SY5Y cells and involved in vesicular release stimulated by acidification. N-type calcium channels may be involved in the increase in vesicular release induced by acid. Our results provide a preliminary study on ASICs in SH-SY5Y cells and neurotransmitter release, which helps to further investigate the relationship between ASICs and dopaminergic neurons.


Assuntos
Ativação do Canal Iônico/fisiologia , Canais Iônicos/fisiologia , Prótons , Cálcio/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Humanos , Concentração de Íons de Hidrogênio , Técnicas de Patch-Clamp , Permeabilidade , Potássio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
4.
Nan Fang Yi Ke Da Xue Xue Bao ; 27(12): 1929-31, 2007 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-18159024

RESUMO

OBJECTIVE: To study the findings in radionuclide cisternography in patients with obstructive hydrocephalus following third ventriculostomy. METHODS: Lumbar radionuclide cisternography was performed in 15 patients with obstructive hydro- cephalus before and after third ventriculostomy. RESULTS: The postoperative cisternography identified radiopharmaceutical reflux into the lateral cerebral ventricles with delayed clearance for 24 h, similar to the findings by cisternography of communicating hydrocephalus. CONCLUSION: The cause of ventricular radiopharmaceutical reflux is not yet understood, possibly in association with the reversal of normal cerebrospinal fluid flow though the fenestration on the third ventrical floor.


Assuntos
Hidrocefalia/diagnóstico por imagem , Terceiro Ventrículo/cirurgia , Ventriculostomia/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Radioisótopos , Cintilografia , Terceiro Ventrículo/diagnóstico por imagem , Adulto Jovem
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