Overexpression of NRF1 alleviates mitochondrial and cognitive dysfunction in mice models of Alzheimer's disease
10.19405/j.cnki.issn1000-1492.2024.02.020
- VernacularTitle:过表达NRF1减轻阿尔茨海默病模型小鼠的线粒体和认知功能障碍
- Author:
Lining SU
1
;
Yanbing WANG
;
Yongcai ZHANG
Author Information
1. 河北北方学院基础医学院,张家口 075000
- Keywords:
Alzheimer's disease;
hippocampus;
nuclear respiratory factor 1;
mitochondria;
cognitive function;
gene therapy
- From:
Acta Universitatis Medicinalis Anhui
2024;59(2):304-309
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of nuclear respiratory factor 1(NRF1)on mitochondrial and cog-nitive dysfunction in Alzheimer's disease(AD)model mice.Methods The 5 × FAD mice were utilized as a mod-el for Alzheimer's disease,and the sparsely labeled AAV virus overexpressing NRF1(AAV-NRF1)was adminis-tered via stereotaxic injection into the brain.The expression of NRF1 in hippocampus was determined by Western blot,the morphology of mitochondria in hippocampus was observed by transmission electron microscope,the den-dritic spines of sparsely labeled neurons in the CA1 region were visualized and quantified using confocal laser mi-croscopy,cognitive and memory functions of mice were evaluated using the Morris water maze test,while electro-physiological methods were employed to detect long-term potentiation(LTP)of synaptic efficacy.Results The ex-pression of NRF1 in the hippocampus was significantly upregulated following stereotactic injection of AAV-NRF1(P＜0.001).This intervention led to notable improvements in mitochondrial morphology within hippocampal neurons,as well as enhanced cognitive and memory functions in mice(P＜0.01).Moreover,there was a significant in-crease in dendritic spine density among neurons located in the CA1 region of the hippocampus(P＜0.001),ac-companied by long-lasting and stable long-term potentiation(LTP)and a substantial elevation in fEPSP slope(P＜0.01).Conclusion The overexpression of NRF1 in a 5 × FAD mouse model of Alzheimer's disease(AD)initia-ted the restoration of mitochondrial dysfunction and enhanced synaptic plasticity,indicating that these alterations may contribute to the therapeutic efficacy of NRF1 overexpression in ameliorating cognitive dysfunction associated with AD.
