Early weaning impairs fear extinction and decreases brain-derived neurotrophic factor expression in the prefrontal cortex of adult male C57BL/6 mice.

We examined the developmental effects of early weaning on anxiety and the extinction of fear memory in male C57BL/6 mice. Early weaning led to increased freezing behaviors after fear conditioning via the foot-shock method both during extinction training and in a test of extinction recall, but did not induce significant changes in anxiety-like behavior. In addition, we found that the levels of brain-derived neurotrophic factor (BDNF) protein and mRNA transcripts for BDNF exon III in the medial prefrontal cortex (mPFC) at the time of extinction recall were impaired in early-weaned mice compared to normally weaned mice. In light of consistent finding that early-weaned mice experience greater stress at weaning, these data suggest that early weaning of male C57BL/6 mice is valuable for studies of the pathogenesis of post-traumatic stress disorder.

Low maternal licking/grooming stimulation increases pain sensitivity in male mouse offspring.

Deprivation of maternal care has been associated with higher pain sensitivity in offspring. In the present study, we hypothesized that the maternal licking/grooming behavior was an important factor for the development of the pain regulatory system. To test this hypothesis, we used male F2 offspring of early-weaned (EW) F1 mother mice that exhibit lower frequency of licking/grooming behavior. The formalin test revealed that F2 offspring of EW F1 dams showed significantly higher pain behavior than F2 offspring of normally-weaned (NW) F1 dams. We found that the mRNA levels of transient receptor potential vanilloid 1 (TRPV1), a nociceptor, were higher in the lumbosacral dorsal root ganglion (DRG) of F2 offspring of EW F1 dams than those of F2 offspring of NW F1 dams, suggesting that the higher pain sensitivity may be attributed to low licking/grooming, which may result in developmental changes in nociceptive neurons. In the DRG, mRNA levels of Mas-related G-protein coupled receptor B4 (MrgprB4), a marker of sensory neurons that detect gentle stroking, was also up-regulated in the F2 offspring of EW F1 dams. Considering that gentle touch alleviates pain, Mrgprb4 up-regulation may reflect a compensatory change. The present findings indicate important implications of maternal licking/grooming behavior in the development of the pain regulatory system.

Low maternal care enhances the skin barrier resistance of offspring in mice.

Deprivation of maternal care via lack of somatosensory input causes offspring to experience adverse consequences, especially in the central nervous system. However, little is known about the developmental effect of maternal care on peripheral tissues such as the skin, which includes cutaneous sensory neurons. In the present study, we examined the involvement of maternal care in the development of the skin. We investigated offspring reared by early-weaned mother mice who spontaneously showed lower frequency of licking/grooming on nursing. Offspring of early-weaned mothers showed higher resistance against skin barrier disruption than did offspring of normally-weaned mothers, and had normal skin barrier function in the intact trunk skin. In the dorsal root ganglion of early-weaned mother offspring, we also found up-regulation of mRNA levels of the Mas-related G-protein coupled receptor B4 (MrgprB4), which is a marker of sensory neurons that detect gentle stroking. We further found that levels of MrgprB4 mRNA were correlated with the enhancement of skin resistance. The present findings suggest that maternal somatosensory inputs have a developmental impact on the cutaneous sensory neurons of the skin in offspring. Interestingly, the present results suggest that lower maternal care has a benefit on the skin resistance. This provides important information for understanding the development of peripheral tissues in offspring reared under severe conditions such as lower maternal care in the wild.