抄録
Although an early adversity is a major risk factor for the vulnerability to stress later in life, the mechanism of the stress vulnerability remains to be unknown. It is known that while neonatal isolation (NI) induces stress vulnerability in adult rats, environmental enrichment (EE) following NI leads to resilience. We examined whether NI induced the susceptibility to learned helplessness (LH) (animal model of depression) and EE ameliorated this susceptibility. Pups were individually isolated from postnatal day 2 to 9. After weaning, EE was administrated until the beginning of LH session. In adulthood, we measured the number of escape failures and escape latency 24 hours after exposure to inescapable shock session. Behavioral analyses revealed that whereas the population of LH in NI rats was significantly higher than that in sham rat, EE markedly decreased the population of LH in NI rats. We tried to identify genes involved in the molecular mechanism underlying the susceptibility to LH using a cDNA array, and real-time PCR. The comparison of hippocampal gene expression between NI-LH and sham-nonLH rats revealed the significant decrease in LIMK1 mRNA in NI-LH. EE prevented the decrease in the expression of LIMK mRNA in the hippocampus of NI rats. These findings suggest that LIMK may play an important role in stress vulnerability developed by an early environment. [J Physiol Sci. 2006;56 Suppl:S25]
