Sex differences in stress coping and anxiety: role of the brain CRF system

在英属哥伦比亚大学Victor Viau博士的实验室进行研究期间，我将研究促肾上腺皮质激素释放因子（CRF）系统在应激应对中的性别特异性作用，以及对反复应激源暴露的习惯过程，以及CRF系统对雌雄大鼠焦虑相关行为的性别特异性调节。迄今为止，大多数神经科学研究都集中在男性身上。然而，越来越多的证据表明，女性发病的几率更高。这种两性二态性在压力的背景下尤其普遍，我在博士论文中已经开始讨论这个问题了。我证明了雌性大鼠对CRF的反应更敏感，表现出比雄性大鼠更多的焦虑相关行为。此外，众所周知，雌性对反复应激源的适应程度较低，这很可能是基于性腺激素和中枢神经肽系统的不同表达。这导致了我的假设，即CRF系统作为压力轴的主要发起者，在压力习惯化和焦虑表达的过程中起着核心和性形态的作用。在Viau博士的实验室进行博士后研究期间，我的目标是通过神经解剖学结合神经药理学和神经内分泌的方法来解决这些问题，从而引出这两个研究问题的潜在机制。

During my research stay in the laboratory of Dr. Victor Viau at the University of British Columbia I will investigate the sex-specific role of the corticotropin-releasing factor (CRF) system in stress coping and the process of habituation to repeated stressor exposition as well as the sex-specific regulation of anxiety-related behavior by the CRF system in male and female rats. To date, most neuroscientific research has focused on males. However, accumulating evidence points to a higher prevalence of females to develop pathophysiologies. This sexual dimorphism is particularly prevailing in the context of stress, which I started to address already in my PhD thesis. I demonstrated that female rats respond more sensitive to CRF and show increased anxiety-related behavior than male rats. Furthermore, it is known that females adapt less to repeated stressor exposition which is most likely based on the distinct expression of gonadal hormones and central neuropeptide systems. This leads to my hypothesis stating that the CRF system as main initiator of the stress axis plays a central and sexually dimorph role in the process of habituation to stress and the expression of anxiety. During my postdoctoral research stay in the laboratory of Dr. Viau, I aim to address these questions via neuroanatomical combined with neuropharmacological and neuroendocrine approaches eliciting potential mechanisms underlying both research questions.