Early maternal separation induces cognitive deficits in adult rats via the dysregulation of hippocampal neuronal nitric oxide synthase expression / 中国神经精神疾病杂志

ABSTRACT

Objective To investigate the effect of maternal separation (MS) on cognitive function in adult male rats through the expression of neuronal nitric oxide synthase (nNOS) in hippocampus, and to reveal the roles of early life stress (ELS) on neural development in rats. Methods Healthy SD pregnant rats (n=12) were randomly divided into maternal separation group (MS group) and control group (NMS group) (n=6 for each group). The newborn rats in the MS group were separated from the mother rats for 3 h every day from postnatal day 3 to 22 whereas no intervention was taken in the NMS group. At the age of 10 weeks, Morris water maze was used to test the learning and memory abilities of two groups of offspring male rats. Neuron immunofluorescence staining was used to examine the number and distribution of neurons in dentate gyrus (DG) of two groups of offspring male rats. Western Blot method was used to detect nNOS, eNOS, Bax/BCL2, Caspase-3 and P53 levels in the hippocampus of the two groups. Ki67/DCX immunofluorescence staining were used to examine the proliferation and differentiation of neurons in the DG area of the hippocampus. TUNEL staining was used to detect the neuronal degeneration and death in the DG area of the hippocampus. Results Behavioral tests showed that the escape latency of male rats in MS group was prolonged, the target quadrant residence time and the number of platform crossing decreased (P<0.05) compared with NMS group. Compared with NMS group, the number of normal and degenerated neurons in hippocampal DG area of MS group had no significant change (P＞0.05). However, the expression of nNOS and eNOS in hippocampus was decreased (P<0.05) and the expression of Bax/BCL2 was increased (P<0.05), but the expression of caspase-3 and P53 remained unchanged (P＞0.05). In addition, Neuronal proliferation and differentiation were decreased and apoptosis was increased in MS group (P<0.05). Conclusion Repeated MS reduces the expression levels of nNOS in the hippocampus, affects the neuronal function in the DG area, and has a long-term influence on the neurodevelopment, which results in cognitive deficits related to learning and memory abilities in adult rats.