Effect of Prenatal Inflammation on Hippocampal Glutamate Receptor 1 Level in the Middle-Aged Mice and the Correlation with Learning and Memory

Abstract

Abstract: Objective: Prenatal inflammation can affect the development of the offspring's physiological system, resulting in many neuropsychiatric conditions, such as neurodevelopmental disorders. Synaptic plasticity is the basis of learning and memory in the central nervous system. Alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid receptors (AMPAR) is an ionic glutamate receptor in the mammalian central nervous system, mediating the delivery of excitatory neurotransmitters, which plays a crucial role in long-term potentiation considered as molecular associations of learning and memory. Studies have suggested that inflammatory cytokines reduce the phosphorylation of AMPAR subunit GluR1 and the surface expression of GluR1, affecting the process of memory consolidation. Therefore, this study aimed to investigate the effect of prenatal inflammation on hippocampal AMPAR subunit GluR-1 in the middle-aged mice and the correlation with learning and memory.

Methods: Maternal mice were intraperitoneally injected with LPS (50 μg/kg) or normal saline at days 15-17 of pregnancy, and their offspring were named as LPS group and control group respectively. The spatial ability of learning and memory was examined with Morris water maze at the ages of 3 months and 15 months at each group. The level of GluR-1 was measured using Western blotting.

Results: The 15-month control group (compared to the 3-month control group) and the 15-month LPS group (compared to the 15-month control group) had significantly longer learning swimming distance (P = 0.014 and 0.011), and lower memory percentage of swimming distance in the target quadrant (P = 0.021 and 0.014) in the Morris water maze, and significantly lower levels of hippocampal GluR-1 (Ps< 0.001). Correlation analysis showed that only the hippocamppal level of GluR-1 in the 15-month mice negatively correlated with swimming distance and positively correlated with the percentage of swimming distance in target quadrant.

Conclusion: Our results suggested that the middle-aged CD-1 mice had decreased GluR-1 content in hippocampus, which correlated with impaired ability of spatial learning and memory, and maternal exposure to inflammation in the late pregnancy accelerated this change.