Inflammatory insult during pregnancy accelerates age-related behavioral and neurobiochemical changes in CD-1 mice

• Published in: AGE Vol. 38; no. 3; p. 59
• Main Authors: Li, Xue-Yan, Wang, Fang, Chen, Gui-Hai, Li, Xue-Wei, Yang, Qi-Gang, Cao, Lei, Yan, Wen-Wen
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2016; Springer Nature B.V
• Subjects: Age; Aging; Aging - metabolism; Alzheimer's disease; Animal cognition; Animals; Anxiety; Behavior; Behavior, Animal; Biomarkers - metabolism; Biomedical and Life Sciences; Brain; Cell Biology; Cognition Disorders - etiology; Cognition Disorders - metabolism; Cognition Disorders - psychology; Cytokines; Dementia; Disease Models, Animal; Female; Females; Geriatrics/Gerontology; Hospitals; Hypertension; Immunohistochemistry; Infections; Inflammation; Inflammation - complications; Inflammation - metabolism; Life Sciences; Male; Memory; Memory - physiology; Mice; Molecular Medicine; Mothers; Neurogenesis; Neurology; Older people; Postpartum period; Pregnancy; Pregnancy Complications, Infectious; Pregnancy, Animal; Stroke - complications; Stroke - metabolism; Stroke - psychology; Pregnancy; Aging; Behaviors; Lipopolysaccharide; Neurobiochemistry; Epigenetic
• DOI: 10.1007/s11357-016-9920-3
• ISSN: 0161-9152; 2509-2715

Data shows that inflammation during pregnancy significantly exerts a long-term influence on offspring, such as increasing the risk of adult cognition decline in animals. However, it is unclear whether gestational inflammation affects the neurobehavioral and neurobiochemical outcomes in the mother-self during aging. In this study, pregnant CD-1 mice intraperitoneally received lipopolysaccharide (LPS) in two doses (25 and 50 g/kg, respectively) or normal saline daily during gestational days 15–17. At the age of 15 months, a battery of behavioral tasks was employed to evaluate their species-typical behaviors, sensorimotor ability, anxiety levels, and spatial learning and memory abilities. An immunohistochemical method was utilized preliminarily to detect neurobiochemical indicators consisting of amyloid-β, phosphorylated tau, presynaptic proteins synaptotagmin-1 and syntaxin-1, glial fibrillary acidic protein (GFAP), and histone-4 acetylation on the K8 site (H4K8ac). The behavioral results showed that LPS exposure during pregnancy exacerbated a decline in 15-month-old CD-1 mice’s abilities to nest, their sensorimotor and spatial learning and memory capabilities, and increased their anxiety levels. The neurobiochemical results indicated that gestational LPS exposure also intensified age-related hippocampal changes, including increased amyloid-β 42 , phosphorylated tau, synaptotagmin-1 and GFAP, and decreased syntaxin-1 and H4K8ac. Our results suggested that the inflammatory insult during pregnancy could be an important risk factor for the development of Alzheimer’s disease, and the H4K8 acetylation might play an important role in the underlying mechanism. This study offers a perspective for improving strategies that support healthy development and successful aging.