Sex-Dependent Effects of Mild Blast-induced Traumatic Brain Injury on Corticotropin-releasing Factor Receptor Gene Expression: Potential Link to Anxiety-like Behaviors
Sex-Dependent Effects of Mild Blast-induced Traumatic Brain Injury on Corticotropin-releasing Factor Receptor Gene Expression: Potential Link to Anxiety-like Behaviors
复制标题
DOI：
10.1016/j.neuroscience.2018.09.014
复制
发表时间：
2018-11-10
期刊：
影响因子：
3.3
通讯作者：
Wu, T. John
中科院分区：
文献类型：
--
作者：
Russell, Ashley L.;Handa, Robert J.;Wu, T. John
创伤性脑损伤（TBI）每年影响美国170万人，导致死亡和残疾的风险增加。军事人员经历的大部分创伤性脑损伤是由爆炸装置引起的。现役军人特别容易受到轻度爆炸引起的（MB）TBI和相关的长期影响，如焦虑症。此外，女性被诊断患有焦虑相关疾病的风险增加。mbTBI导致男性和女性焦虑症的机制尚不清楚。性二态促肾上腺皮质激素释放因子（CRF）是一种与焦虑有关的大脑信号系统。CRF及其相关肽家族通过与CRF受体亚型1和2（分别为CRFR1、CRFR2）结合来调节焦虑相关行为。这些受体分布在控制与情绪、记忆和唤醒有关的行为的边缘系统结构中。因此，本研究的目的是通过检查mbTBI对雄性和雌性小鼠CRFR系统的影响来了解mbTBI与焦虑之间的联系。mbTBI增加了男性和女性的焦虑样行为（p < 0.05）。在本研究中，mbTBI没有改变男性或女性的CRFR1基因表达。然而，mbTBI破坏了男性和女性不同边缘结构中的CRFR2基因表达。在男性中，mbTBI增加了腹侧海马中的基线CRFR2基因表达（p < 0.05），并降低了终纹前床核（aBNST）和杏仁核中的限制诱导的表达（p < 0.05）。在雌性中，mbTBI降低背侧海马中限制诱导的CRFR2基因表达（p < 0.05）。固有的性别差异和mbTBI诱导的限制诱导的CRFR2基因表达的减少可能有助于焦虑样行为。本研究的结果表明，边缘系统结构内的mbTBI的反应调制焦虑的性别依赖性的方式。这些研究进一步表明，CRFR2可以作为减轻mbTBI效应的潜在靶标。由Elsevier Ltd代表IBRO出版。
Traumatic brain injury (TBI) affects 1.7 million people in the United States every year, resulting in increased risk of death and disabilities. A significant portion of TBIs experienced by military personnel are induced by explosive blast devices. Active duty military personnel are especially vulnerable to mild blast-induced (mb)TBI and the associated long-term effects, such as anxiety disorders. Additionally, females are at an increased risk of being diagnosed with anxiety-related disorders. The mechanism by which mbTBI results in anxiety disorders in males and females is unknown. The sexually dimorphic corticotropin-releasing factor (CRF) is a brain signaling system linked to anxiety. CRF and its family of related peptides modulate anxiety-related behaviors by binding to CRF receptor subtypes 1 and 2 (CRFR1, CRFR2, respectively). These receptors are distributed throughout limbic structures that control behaviors related to emotion, memory, and arousal. Therefore, the aim of this study was to understand the link between mbTBI and anxiety by examining the impact of mbTBI on the CRFR system in male and female mice. mbTBI increased anxiety-like behaviors in both males and females (p < 0.05). In the present study, mbTBI did not alter CRFR1 gene expression in males or females. However, mbTBI disrupted CRFR2 gene expression in different limbic structures in males and females. In males, mbTBI increased baseline CRFR2 gene expression in the ventral hippocampus (p < 0.05) and decreased restraint-induced expression in the anterior bed nucleus of the stria terminalis (aBNST) and amygdala (p < 0.05). In females, mbTBI decreased restraint-induced CRFR2 gene expression in the dorsal hippocampus (p < 0.05). The inherent sex differences and the mbTBI-induced decrease in restraint-induced CRFR2 gene expression may contribute to anxiety-like behaviors. The results of the present study show that the response to mbTBI within the limbic structures modulates anxiety in a sex-dependent manner. The studies further suggest that CRFR2 may serve as a potential target to mitigate mbTBI effects. Published by Elsevier Ltd on behalf of IBRO.