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Exposure to Stress or an Enriched Environment in Youth Modulates Prenatal Inflammation-Induced Cognitive Deficits in
Yong-Fang Wu1, Lei Cao2, Li-Ping Zeng3
1Department of Rehabilitation Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Introduction:
Brain aging can promote neuronal damage, contributing to aging-associated memory impairments (AAMI), a phenomenon characteristic of normal aging. However, it remains unclear whether and how exposure to stress or an enriched environment (S/E) during youth influences AAMI induced by prenatal inflammation. Therefore, SNAP-25, a key presynaptic membrane protein closely related to cognitive function, was selected as the primary molecular target. This project aimed to investigate the effects and underlying mechanisms of youth stress (S) and enriched environment (E) on the AAMI induced by prenatal inflammation.
Methods:
Lipopolysaccharide (LPS) injection was used to establish an animal model of prenatal inflammation. Two experimental techniques, including S and E, were applied. The male offspring mice were randomly divided into four groups: LPS+S, LPS+E, LPS, and NS. Cognitive function was assessed using the Morris water maze test, while hippocampal synaptosomal-associated protein 25 (SNAP-25) expression was examined using Western blot and RNA in situ hybridization (RNAscope) techniques.
Results:
Young mice (3 months old) exhibited better cognitive function and lower SNAP-25 expression compared with middle-aged mice (15 months old), indicating that the middle-aged mice displayed the expected impairment in spatial cognitive ability. Furthermore, LPS significantly impaired memory performance and increased SNAP-25 expression, whereas exposure to stress or an enriched environment (S/E) alleviated AAMI. In addition, a significant correlation was observed between SNAP-25 expression and cognitive performance.
Conclusion:
Youth exposure to stress or an enriched environment (S/E) at 2 months of age modulated the expression level of hippocampal SNAP-25 induced by prenatal inflammation. Moreover, increased SNAP-25 expression was associated with memory impairment.
