Depression-like Behavior and Change in Hippocampus BDNF mRNA Expression Induced by Early Deprivation in Rats

Abstract

There is considerable evidence that adverse early life events have profound and persistent effects on brain functions and may represent a risk factor for the development of depression later in life. Studies of postnatalenvironmental manipulations in rodents can potentially yield evidence that adverse early-life experience leading to behavior dysfunction is a general mammalian characteristic, and this approach can be used to develop animal models for depression research to explore its neurobiology mechanism. To investigate the long-term effects of early deprivation (ED) on behavior and expression of brain-derived neurotrophic factor (BDNF) in adult rats, the new-born Sprague-Dawley pups were randomly divided into non-handling (NH) group and ED group. Pups in ED group were isolated from dam, nest and littermates daily for 4 hours from the post-natal day (PND) 1 to PND14 while pups in NH group were undisturbed at room ambient temperature of 21°C. Body weights were monitored after weaning and sucrose preference test was carried out from PND36 to PND64 once a week (n=16). At 12 weeks of age, rats were subjected to behavioral sessions for the foot-shock pre-exposure/shuttle box test (n=8), the contents of BDNF in hippocampus were measured by enzyme-linked immunosorbent assay (n=8) and hippocampus BDNF mRNA expression was detected by in situ hybridization (n=6). Body weights of ED rats were significantly lower than NH rats (p0.01), sucrose intake and sucrose preference were significantly decreased in ED rats compared with NH rats (p0.05 or p0.01). In contrast to NH rats, ED rats performed less barrier crossings in the training session of shuttle box test (p0.05), but in the testing session, comparison of the manipulation groups yielded no significant differences. The contents of BDNF in hippocampus and the BDNF mRNA expression in CA1and CA3 of ED rats were decreased significantly (p0.05 or p0.01). The results suggest that ED may result in the decrease of growth, the depression-like behavior of anhedonia, and the reduction of hippocampus BDNF mRNA expression in Sprague-Dawley rats, but did not induce the behavior of learned helplessness in a foot-shock pre-exposure/shuttle box test. The reduction of BDNF expression in hippocampus may play a role in the development of depression-like behavior induced by ED.