Reward and immune responses in adolescent females following experimental traumatic brain injury
Reward and immune responses in adolescent females following experimental traumatic brain injury
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DOI：
10.1016/j.bbr.2019.112333
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发表时间：
2020-02-03
影响因子：
2.7
通讯作者：
Ramirez, Servio H.
中科院分区：
文献类型：
--
作者：
Cannella, Lee Anne;Andrews, Allison M.;Ramirez, Servio H.
创伤性脑损伤（TBI）的病理对许多脑区域产生不利影响，经常导致包括物质使用障碍（SUD）在内的共病性精神疾病的发展。虽然传统上认为这是一种主要影响男性的流行病，但最近的临床研究报告称，女性脑震荡的发病率高于男性，康复时间也比男性长。然而，神经创伤，特别是大脑深处的神经创伤，在两性之间是如何不同地表现出来的，在很大程度上仍然是未知的。脑外伤的风险在青春期达到顶峰，此时调节奖赏行为的神经网络还没有完全发育。先前，我们使用条件位置偏好（CPP）测定，发现青春期脑外伤增加了雄性小鼠对可卡因奖励效应的敏感性。此外，我们观察到炎症谱增强，神经元蛋白的小胶质细胞吞噬增加，NAc中神经元棘密度降低。值得注意的是，尚未调查脑外伤后SUD易感性的性别差异程度。因此，在这里，我们提出一个核心问题，即青少年tbi诱导的奖励中心的神经炎症特征是否以性别依赖的方式存在差异。通过CPP分析，我们发现青春期脑外伤时雌性性激素水平高的雌性小鼠表现出神经保护作用，对可卡因奖励效应的敏感性增加。这些研究也提供了证据，表明在雌性NAc内，小胶质细胞的激活和神经元蛋白的吞噬作用显著降低。总的来说，我们的研究结果为青少年脑外伤如何以性别依赖的方式影响奖励通路提供了重要的见解，这可以解释成瘾行为的脆弱性。
The pathology of traumatic brain injury (TBI) adversely affects many brain regions, often resulting in the development of comorbid psychiatric disorders including substance use disorders (SUD). Although traditionally thought to be an epidemic that predominantly affects males, recent clinical studies report females have higher rates of concussions and longer recovery times than males. Yet, how neurotrauma, particularly deep within the brain, between the sexes is differentially manifested remains largely unknown. The risk of TBI peaks during adolescence when neuronal networks that regulate reward behaviors are not fully developed. Previously, using the conditioned place preference (CPP) assay, we found that adolescent TBI increased susceptibility to the rewarding effects of cocaine in male mice. Further, we observed augmented inflammatory profiles, increased microglial phagocytosis of neuronal proteins, and decreased neuronal spine density in the NAc. Notably, the extent of sex differences in SUD susceptibility following TBI has not be investigated. Thus, here we ask the central question of whether the adolescent TBI-induced neuroinflammatory profile at reward centers is divergent in a sex-dependent manner. Using the CPP assay, we found that female mice with high levels of female sex hormones at the time of adolescent TBI demonstrated neuroprotection against increased sensitivity to the rewarding effects of cocaine. These studies also provide evidence of significantly reduced microglial activation and phagocytosis of neuronal proteins within the NAc of females. Overall, our results offer crucial insight into how adolescent TBI impacts the reward pathway in a sex depending manner that could explain a vulnerability to addiction-like behavior.