Desbonnet Lieve, Garrett Lillian, Daly Emma, McDermott Kieran W, Dinan Timothy G
Department of Psychiatry and Alimentary Pharmacobiotic Centre, University College Cork, Cork, Ireland.
Int J Dev Neurosci. 2008 May-Jun;26(3-4):259-68. doi: 10.1016/j.ijdevneu.2008.02.004. Epub 2008 Mar 10.
Neonatal maternal separation has been widely used to model the well-established causal relationship between stress in early life and the later development of depression. As corticotrophin-releasing factor (CRF) and vasopressin (AVP) have been implicated in depression, we aimed to determine the long-term effects of maternal separation stress on these neuropeptide systems, and also to explore whether these effects are gender-dependent. Immunohistochemical staining of CRF, AVP and c-Fos was used to assess whether these neuropeptide systems were affected following an acute swim stress in male and female maternally separated rats. There was an increase in CRF-immunoreactivity (IR) (p<0.05), and an increased co-localisation of c-Fos and CRF (p<0.05) following stress, in the paraventricular nucleus of the hypothalamus (PVN) of maternally separated female rats only. We found no differences in CRF in the hypothalamus of maternally separated and control male rats. However, male maternally separated rats exhibited decreases in AVP-IR in both the non-stressed and stressed groups relative to controls (p<0.001). These data provide further evidence of the involvement of the neuropeptides CRF and AVP in the long-term maladaptive effects of maternal separation stress in early life. The enhanced CRF response to stress in MS females relative to males suggests that maternal separation stress results in a more reactive neuroendocrinological stress system in females, than in males. Furthermore, the sexually dimorphic effects of maternal separation on these neuropeptides indicate that gender is an important factor influencing the trajectory of early life stress effects on CRF and AVP systems in the brain.
新生期母婴分离已被广泛用于模拟早期生活压力与后期抑郁症发展之间已确立的因果关系。由于促肾上腺皮质激素释放因子（CRF）和血管加压素（AVP）与抑郁症有关，我们旨在确定母婴分离应激对这些神经肽系统的长期影响，并探讨这些影响是否存在性别依赖性。采用CRF、AVP和c-Fos的免疫组织化学染色来评估雄性和雌性母婴分离大鼠在急性游泳应激后这些神经肽系统是否受到影响。仅在母婴分离的雌性大鼠下丘脑室旁核（PVN）中，应激后CRF免疫反应性（IR）增加（p<0.05），且c-Fos与CRF的共定位增加（p<0.05）。我们发现母婴分离的雄性大鼠与对照雄性大鼠下丘脑的CRF无差异。然而，与对照组相比，母婴分离的雄性大鼠在非应激组和应激组中AVP-IR均降低（p<0.001）。这些数据进一步证明了神经肽CRF和AVP参与了早期生活中母婴分离应激的长期适应不良效应。与雄性相比，母婴分离的雌性大鼠对应激的CRF反应增强，这表明母婴分离应激导致雌性比雄性具有更活跃的神经内分泌应激系统。此外，母婴分离对这些神经肽的性别差异效应表明，性别是影响早期生活应激对大脑中CRF和AVP系统作用轨迹的重要因素。
