Maternal chewing alleviates prenatal stress-related neuroinflammation mediated by microglia in the hippocampus of the mouse offspring.

PURPOSE: Prenatal stress affects the hippocampal structure and function in pups. Maternal chewing ameliorates hippocampus-dependent cognitive impairments induced by prenatal stress. In this study, we investigated hippocampal microglia-mediated neuroinflammation in pups of dams exposed to prenatal stress with or without chewing during gestation. METHODS: Pregnant mice were randomly assigned to control, stress, and stress/chewing groups. Stress and stress/chewing animals were subjected to restraint stress for 45 min three times daily from gestation day 12 to parturition, and were given a wooden stick to chew during the stress period. Four-month-old male pups were intraperitoneally administered with lipopolysaccharide (LPS). Serum corticosterone levels were determined 24 h after administration. The expression levels of hippocampal inflammatory cytokines were measured, and the microglia were analyzed morphologically. RESULTS: Prenatal stress increased serum corticosterone levels, induced hippocampal microglia priming, and facilitated the release of interleukin-1ß and tumor necrosis factor-α in the offspring. LPS treatment significantly increased the effects of prenatal stress on serum corticosterone levels, hippocampal microglial activation, and hippocampal neuroinflammation. Maternal chewing significantly inhibited the increase in serum corticosterone levels, suppressed microglial overactivation, and normalized inflammatory cytokine levels under basal prenatal stress conditions as well as after LPS administration. CONCLUSIONS: Our findings indicate that maternal chewing can alleviate the increase in corticosterone levels and inhibit hippocampal microglia-mediated neuroinflammation induced by LPS administration and prenatal stress in adult offspring.

Maternal chewing improves prenatal stress-induced cognitive deficit and anxiety-like behavior associated with alterations of the apoptotic response and serotonin pathway in mouse offspring.

OBJECTIVE: To examine whether maternal chewing affects prenatal stress-induced behavioral alternations associated with the changes in apoptosis-related proteins and serotonin pathway of the mouse offspring. DESIGN: Pregnant mice were assigned to control, stress, and stress/chewing groups. Stress mice were placed in restraint tubes, from gestational day 12 until parturition. Stress/chewing mice were given a wooden stick for chewing during stress period. Morris water maze and hole-board tests were applied for behavioral alterations in one-month-old male pups. Hippocampal mRNA expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax) was analyzed by quantitative real-time PCR. Serotonin and tryptophan hydroxylase expression level in the dorsal raphe nucleus was investigated immunohistochemically. RESULTS: Prenatal stress impaired the spatial learning, induced anxiety-like behavior, increased the ratio of hippocampal Bax/Bcl-2 expression, and decreased the expression of serotonin and tryptophan hydroxylase in dorsal raphe nucleus of the offspring. Maternal chewing ameliorated prenatal stress-induced cognitive impairment, anxiety-like behavior, and attenuated the increased ratio of hippocampal Bax/Bcl-2 expression, and the downregulated serotonin signaling in dorsal raphe nucleus of the offspring. CONCLUSIONS: Our results indicate that maternal chewing could improve prenatal stress-related anxiety-like behavior and cognitive impairment in mouse offspring, at least in part by affecting hippocampal apoptotic response and central serotonin pathway.