Chewing during prenatal stress prevents prenatal stress-induced suppression of neurogenesis, anxiety-like behavior and learning deficits in mouse offspring

Abstract

Prenatal stress (PS) induces learning deficits and anxiety-like behavior in mouse pups by increasing corticosterone levels in the dam. We examined the effects of maternal chewing during PS on arginine vasopressin (AVP) mRNA expression in the dams and on neurogenesis, brain-derived neurotrophic factor (BDNF) mRNA expression, learning deficits and anxiety-like behavior in the offspring. Mice were divided into control, stress and stress/chewing groups. Pregnant mice were exposed to restraint stress beginning on day 12 of pregnancy and continuing until delivery. Mice in the stress/chewing group were given a wooden stick to chew during restraint stress. PS significantly increased AVP mRNA expression in the paraventricular nucleus (PVN) of the hypothalamus in the dams. PS also impaired learning ability, suppressed neurogenesis and BDNF mRNA expression in the hippocampus, and induced anxiety-like behavior in the offspring. Chewing during PS prevented the PS-induced increase in AVP mRNA expression of the PVN in the dams. Chewing during PS significantly attenuated the PS-induced learning deficits, anxiety-like behavior, and suppression of neurogenesis and BDNF mRNA expression in the hippocampus of the offspring. Chewing during PS prevented the increase in plasma corticosterone in the dam by inhibiting the hypothalamic-pituitary-adrenal axis activity, and attenuated the attenuated the PS-induced suppression of neurogenesis and BDNF expression in the hippocampus of the pups, thereby ameliorating the PS-induced learning deficits and anxiety-like behavior. Chewing during PS is an effective stress-coping method for the dam to prevent PS-induced deficits in learning ability and anxiety-like behavior in the offspring.

Effects of Maternal Chewing on Prenatal Stress-Induced Cognitive Impairments in the Offspring via Multiple Molecular Pathways

“…Animal studies demonstrate that prenatal restraint stress suppresses hippocampal neurogenesis and results in anxiety-and depressive-like behavior and learning disorders in the offspring [48][49][50]. Our findings that maternal chewing during prenatal stress markedly alleviated the neurogenesis impairment in the hippocampal DG in offspring mice are consistent with previous findings [18,20]. BDNF, as the most abundant neurotrophin in the brain, contributes to enhancing synaptic plasticity and improving cognitive functions such as learning, memory and higher thinking [51].…”

“…Consistent with previous reports, allowing pregnant mice to chew on a wooden stick during prenatal restraint stress ameliorated the spatial learning impairment induced in the offspring [18,20,21]. Hippocampal neurogenesis highly modulates cognitive processes such as learning, memory and anxiety by regulating information processing in the hippocampal DG [44,45].…”

“…BDNF-GC equilibrium is crucial throughout life as a major mechanism for stress response regulation [36]. Prenatal stress downregulates hippocampal BDNF [18] and GR expression [19]. The combination of low BDNF and low GR expression results in vulnerability to stress-related disorders.…”

“…The prenatal restraint stress procedure was performed as previously described [18,20,21]. Briefly, pregnant mice in the STRESS and STRESS + CHEWING groups were placed in a ventilated plastic transparent cylinder (4.5 cm diameter, 10.3 cm long), in which the pregnant mice could move back and forth but not turn around, 3 times daily for 45 min each at 09:00, 13:00 and 17:00, from gestational day 12 until parturition.…”

“…In rodents, chewing during restraint stress alleviates anxiety-like behavior and cognitive impairments induced by restraint stress [16,17]. Maternal chewing also ameliorates prenatal stress-induced spatial learning impairment and deficiencies in hippocampal neurogenesis, myelination and synaptic plasticity in the offspring [18][19][20][21], but the underlying mechanisms have remained unclear.…”