Sirt1 protects against hippocampal atrophy and its induced cognitive impairment in middle-aged mice

• Published in: BMC neuroscience 2022-06, Vol.23 (1), p.33-33, Article 33
• Main Authors: Sun, Zuhao, Zhao, Shuang, Suo, Xinjun, Dou, Yan
• Format: Article
• Language: English
• Subjects: Aging; Alzheimer's disease; Atrophy; Behavior; Brain; Brain structural MRI; Cognition & reasoning; Cognition disorders; Cognitive ability; DNA methylation; Efficiency; Epitopes; Exploratory behavior; Gene expression; Genetic aspects; Glutamic acid receptors; Health aspects; Hippocampal atrophy; Hippocampus; Hippocampus (Brain); Learning and memory; Magnetic resonance imaging; Memory; Middle age; Molecular modelling; N-Methyl-D-aspartic acid receptors; Neuroimaging; Open-field behavior; Patient outcomes; Phenotypes; Phosphorylation; Physiological aspects; Plasmids; Postsynaptic density proteins; Proteins; Psychological aspects; Risk factors; Sirt1; SIRT1 protein; Spatial discrimination learning; Spatial memory; Tau protein; Therapeutic targets; Western blotting
• ISSN: 1471-2202; 1471-2202
• DOI: 10.1186/s12868-022-00718-8

Sirtuin 1 (Sirt1) is a recognized longevity gene and has been shown to be associated with aging and its related diseases. Hippocampal volume is considered to be the most sensitive brain imaging phenotype for cognition, but the effect of Sirt1 on hippocampal morphology during aging has not been reported. Herein, we investigated the effect of conditional Sirt1 knockdown on hippocampal volume in middle-aged mice, as well as its cognitive function and the underlying molecular mechanisms. Brain structural magnetic resonance imaging (MRI) showed that adeno-associated virus (AAV) mediated hippocampal Sirt1 knockdown caused hippocampal atrophy in 8-month-old mice. Open field test (OFT) and Morris Water Maze (MWM) test revealed that hippocampal Sirt1 knockdown significantly weakened spatial learning and memory of mice without effect on anxiety and exploratory behavior. Western blotting analysis showed that P-tau levels at serine 396 epitope were significantly increased with slightly decreased T-tau levels, while PSD95 and NMDAR2B levels were obviously reduced, indicating that hippocampal Sirt1 knockdown could activate tau hyperphosphorylation and synaptic damage. This work revealed that Sirt1 is an important protective gene against hippocampal atrophy and its induced cognitive impairment during aging, providing potential therapeutic targets for the prevention and intervention of aging-related neuropsychic diseases.