1. Metformin restores hippocampal neurogenesis and learning and memory via regulating gut microbiota in the obese mouse model
- Author
-
Pei Pang, Feixiao Xue, Xiaoyi Ma, Hao Li, Huanhuan Yan, Wenchang Xiao, Lu Wan, and Lei Pei
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Neurogenesis ,Immunology ,Mice, Obese ,Type 2 diabetes ,Gut flora ,Hippocampal formation ,Diet, High-Fat ,Hippocampus ,Mice ,03 medical and health sciences ,Behavioral Neuroscience ,0302 clinical medicine ,RNA, Ribosomal, 16S ,Internal medicine ,medicine ,Animals ,Obesity ,Cognitive decline ,Neuroinflammation ,biology ,Endocrine and Autonomic Systems ,business.industry ,Dentate gyrus ,biology.organism_classification ,medicine.disease ,Metformin ,Gastrointestinal Microbiome ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Diabetes Mellitus, Type 2 ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Numerous studies have shown that over-nutritional obesity may lead to pre-diabetes, type 2 diabetes and cognitive decline. As the degree of metabolic disorders increases, the cognitive decline is getting worse. However, the cellular events that cause this cognitive dysfunction is yet to be clarified. We used a high-fat diet (HFD) consumption-induced obesity mouse model to test the effects of metformin on the hippocampal neurogenesis and learning and memory abilities of obese mice. 5-Bromo-2'-deoxyuridine (BrdU) labelling and retrovirus labeling were applied to detect hippocampal newborn neurons. Behavioral experiments were used to detect learning and memory abilities of mice. 16S rRNA gene sequencing was performed to detect the composition of gut microbiota. The positron emission tomography (PET) was conducted to detect the energy metabolism activity of different mouse brain regions. Our results reveal that metformin restores the impairment of neurogenesis in the dentate gyrus and finally prevents the cognitive decline of the obese mice. Moreover, the therapeutic effects of metformin are achieved by regulating the composition of gut microbiota of mice, which may inhibit microglia activation and neuroinflammation in the brain of obese mice. This study suggests that metformin may be taken as a promising candidate for the intervention of cognitive decline related to imbalance of gut microbiota caused by obesity.
- Published
- 2021
- Full Text
- View/download PDF