Shu Chang, Xiao Ling, Tang Jihua, Wang Gaohua, Zhang Xueping, Wang Xiaoping
Department of Psychiatry, Renmin Hospital, Wuhan University, Hubei, P.R. China.
Tohoku J Exp Med. 2015 Feb;235(2):81-7. doi: 10.1620/tjem.235.81.
Childhood adversity has profound and persistent effects on brain functions and has been implicated in the etiology of depression. Brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) play critical roles during brain development to maintain neuronal function and structural integrity in adulthood. We therefore investigated the long-term effects of early life adversity on the depression-related behavior and the expression of BDNF and CREB in the hippocampus. Male Sprague-Dawley newborn rats were subjected to maternal separation for 3 h/day on postnatal days 2-14. After the postnatal day 90, rats with or without the experience of infancy maternal separation received a series of unpredictable chronic mild stress (CMS) for 21 days. Sucrose preference and spontaneous activity in the open field test were recorded, and the expression of BDNF and CREB in the hippocampus was measured by real-time RT-PCR and Western blot analyses. Before exposure to CMS, the rats with maternal separation showed the significant decreases in sucrose preference, spontaneous activity, and hippocampal expression of BDNF and CREB, compared to the animals without maternal separation. In contrast, the rats without maternal separation showed greater decreases of the above indictors after CMS, the levels of which were lower than those observed in the rats with maternal separation. Thus, early life adversity leads to long-term decreases in the capacity of enjoying sweetness, spontaneous activity, and hippocampal expression of BDNF and CREB. Moreover, childhood neglect may decrease the neurobehavioral plasticity, thereby blunting the responses to adulthood stress and increasing the susceptibility to depression.
童年逆境对大脑功能有深远且持久的影响，并与抑郁症的病因有关。脑源性神经营养因子（BDNF）和环磷酸腺苷反应元件结合蛋白（CREB）在大脑发育过程中发挥关键作用，以维持成年期的神经元功能和结构完整性。因此，我们研究了早年逆境对抑郁相关行为以及海马体中BDNF和CREB表达的长期影响。将雄性斯普拉-道莱新生大鼠在出生后第2至14天每天进行3小时的母婴分离。在出生后第90天，有或没有婴儿期母婴分离经历的大鼠接受了一系列不可预测的慢性轻度应激（CMS），持续21天。记录蔗糖偏好和旷场试验中的自发活动，并通过实时RT-PCR和蛋白质免疫印迹分析测量海马体中BDNF和CREB的表达。在暴露于CMS之前，与未经历母婴分离的动物相比，经历母婴分离的大鼠在蔗糖偏好、自发活动以及海马体中BDNF和CREB的表达方面均显著降低。相反，未经历母婴分离的大鼠在CMS后上述指标的下降幅度更大，其水平低于经历母婴分离的大鼠。因此，早年逆境导致享受甜味的能力、自发活动以及海马体中BDNF和CREB的表达长期下降。此外，童年期忽视可能会降低神经行为可塑性，从而削弱对成年期应激的反应，并增加患抑郁症的易感性。
