Knock-down of ROCK2 gene improves cognitive function and reduces neuronal apoptosis in AD mice by promoting mitochondrial fusion and inhibiting its division / 细胞与分子免疫学杂志
Chinese Journal of Cellular and Molecular Immunology
; (12): 701-707, 2023.
Artigo
em Chinês
| WPRIM (Pacífico Ocidental)
| ID: wpr-1009420
Biblioteca responsável:
WPRO
ABSTRACT
Objective To explore the effect of knocking down Rho-associated coiled-coil kinase (ROCK2) gene on the cognitive function of amyloid precursor protein/presenilin-1 (APP/PS1) double transgenic mice and its mechanism. Methods APP/PS1 double transgenic mice were randomly divided into AD model group (AD group), ROCK2 gene knock-down group (shROCK2 group), ROCK2 gene knock-down control group (shNCgroup), and wild-type C57BL/6 mice of the same age served as the wild-type control (WT group). Morris water maze and Y maze were employed to test the cognitive function of mice. Neuron morphology was detected by Nissl staining. Immunofluorescence histochemical staining was used to detect the expression of phosphorylated dynamin-related protein 1 (p-Drp1) and mitochondrial fusion 1 (Mfn1). Western blot analysis was used to detect the expression ROCK2, cleaved-caspase-3 (c-caspase-3), B-cell lymphoma 2 (Bcl2), Bcl2-related protein X (BAX), p-Drp1, mitochondrial fission 1 (Fis1), optic atrophy 1 (OPA1), Mfn1 and Mfn2. Results Compared with AD group mice, the expression of ROCK2 in shROCK2 group mice was significantly reduced; the cognitive function was significantly improved with the number of neurons in the hippocampal CA3 and DG areas increasing, and nissl bodies were deeply stained; the expression of c-caspase-3 and BAX was decreased, while the expression of Bcl2 was increased; the expression of mitochondrial division related proteins p-Drp1 and Fis1 were decreased, while the expression of mitochondrial fusion-related proteins OPA1, Mfn1 and Mfn2 were increased. Conclusion Knock-down of ROCK2 gene can significantly improve the cognitive function and inhibit the apoptosis of nerve cells of APP/PS1 mice. The mechanism may be related to promoting mitochondrial fusion and inhibiting its division.
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Camundongos Transgênicos
/
Peptídeos beta-Amiloides
/
Precursor de Proteína beta-Amiloide
/
Apoptose
/
Cognição
/
Modelos Animais de Doenças
/
Proteína X Associada a bcl-2
/
Caspase 3
/
Doença de Alzheimer
/
Dinâmica Mitocondrial
Limite:
Animais
Idioma:
Chinês
Revista:
Chinese Journal of Cellular and Molecular Immunology
Ano de publicação:
2023
Tipo de documento:
Artigo