RESUMO
BACKGROUND: Electroacupuncture (EA) is a complementary and alternative therapy which has shown protective effects on vascular cognitive impairment (VCI). However, the underlying mechanisms are not entirely understood. METHODS: Rat models of VCI were established with cerebral ischemia using occlusion of the middle cerebral artery or bilateral common carotid artery. The brain structure and function imaging were measured through animal MRI. miRNA expression was detected by chip and qPCR. Synaptic functional plasticity was detected using electrophysiological techniques. RESULTS: This study demonstrated the enhancement of Regional Homogeneity (ReHo) activity of blood oxygen level-dependent (BOLD) signal in the entorhinal cortical (EC) and hippocampus (HIP) in response to EA treatment. miR-219a was selected and confirmed to be elevated in HIP and EC in VCI but decreased after EA. N-methyl-D-aspartic acid receptor1 (NMDAR1) was identified as the target gene of miR-219a. miR-219a regulated NMDAR-mediated autaptic currents, spontaneous excitatory postsynaptic currents (sEPSC), and long-term potentiation (LTP) of the EC-HIP CA1 circuit influencing synaptic plasticity. EA was able to inhibit miR-219a, enhancing synaptic plasticity of the EC-HIP CA1 circuit and increasing expression of NMDAR1 while promoting the phosphorylation of downstream calcium/calmodulin-dependent protein kinase II (CaMKII), improving overall learning and memory in VCI rat models. CONCLUSION: Inhibition of miR-219a ameliorates VCI by regulating NMDAR-mediated synaptic plasticity in animal models of cerebral ischemia.
Assuntos
Isquemia Encefálica , Eletroacupuntura , Animais , Ratos , Encéfalo , Fosforilação , HipocampoRESUMO
OBJECTIVE: To explore the precise mechanism of electroacupuncture (EA) to delay cognitive impairment in Alzheimer disease. METHODS: N-Acetylaspartate (NAA), glutamate (Glu) and myoinositol (mI) metabolism were measured by magnetic resonance spectroscopy, learning and memory of APP/PS1 mouse was evaluated by the Morris water maze test and the step-down avoidance test, neuron survival number and neuronal structure in the hippocampus were observed by Nissl staining, and BDNF and phosphorylated TrkB detected by Western blot. RESULTS: EA at DU20 acupuncture significantly improve learning and memory in behavioral tests, up-regulate NAA, Glu and mI metabolism, increase the surviving neurons in hippocampus, and promote the expression of BDNF and TrkB in the APP/PS1 transgenic mice. CONCLUSION: These findings suggested that EA is a potential therapeutic for ameliorate cognitive dysfunction, and it might be due to EA could improve NAA and Glu metabolism by upregulation of BDNF in APP/PS1 mice.
Assuntos
Ácido Aspártico/análogos & derivados , Eletroacupuntura/métodos , Ácido Glutâmico/metabolismo , Hipocampo/química , Aprendizagem/fisiologia , Memória/fisiologia , Animais , Ácido Aspártico/metabolismo , Western Blotting , Fator Neurotrófico Derivado do Encéfalo , Teste de Esforço , Hipocampo/diagnóstico por imagem , Inositol/análise , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Aprendizagem em Labirinto , Glicoproteínas de Membrana/análise , Camundongos , Camundongos Transgênicos , Modelos Animais , Proteínas Tirosina Quinases/análise , Distribuição AleatóriaRESUMO
OBJECTIVE: To explore the precise mechanism of electroacupuncture (EA) to delay cognitive impairment in Alzheimer disease. Methods N -Acetylaspartate (NAA), glutamate (Glu) and myoinositol (mI) metabolism were measured by magnetic resonance spectroscopy, learning and memory of APP/PS1 mouse was evaluated by the Morris water maze test and the step-down avoidance test, neuron survival number and neuronal structure in the hippocampus were observed by Nissl staining, and BDNF and phosphorylated TrkB detected by Western blot. RESULTS: EA at DU20 acupuncture significantly improve learning and memory in behavioral tests, up-regulate NAA, Glu and mI metabolism, increase the surviving neurons in hippocampus, and promote the expression of BDNF and TrkB in the APP/PS1 transgenic mice. CONCLUSION: These findings suggested that EA is a potential therapeutic for ameliorate cognitive dysfunction, and it might be due to EA could improve NAA and Glu metabolism by upregulation of BDNF in APP/PS1 mice.