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

Abstract

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-β42, 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.

Keywords: Aging; Behaviors; Epigenetic; Lipopolysaccharide; Neurobiochemistry; Pregnancy.

Fig. 1

Performances of differently-treated CD-1 mice in the RAWM. The latency (a, b) and number of errors (c, d) during the learning phase (Trials 1–4), the latency (e, f), and number of errors (g, h) during the memory phase (Trial 5). There were significant age and treatment effects on two measures during both the learning and memory phases. The sample number was 40 for the four groups, with 10 mice in each group. The bars standing represented for SEM compared to the Y-con mice ^# P < 0.05 and compared to the O-con mice *P < 0.05

Fig. 2

The p-tau levels in the hippocampal subregions in the differently-treated CD-1 mice. The subregions included dentate gyrus (DG), CA1, and CA3. Data were expressed by mean ± SEM Asterisk denotes the significant difference of the O-con group compared to the Y-con group (*P < 0.05, **P < 0.001). Number sign denotes the significant difference of the comparison between the LPS groups and the O-con group (^# P < 0.05; ^## P < 0.001). AOD average optical density

Fig. 3

The GFAP levels in the hippocampal subregions in the differently-treated CD-1 mice. The other information is identical to Fig. 2

Fig. 4

The H4K8ac levels in the hippocampal subregions in the differently-treated CD-1 mice. The other information is identical to Fig. 2