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.