Oliverio Robin, Fitzgerald Julie, Velazquez-Cruz Ruth, Whitehead Bailey, Karelina Kate, Weil Zachary M
Department of Neuroscience and Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, United States.
Department of Neuroscience, Ohio State University, Columbus, OH, United States.
Front Behav Neurosci. 2022 Jun 21;16:907552. doi: 10.3389/fnbeh.2022.907552. eCollection 2022.
Intoxication is a leading risk factor for injury, and TBI increases the risk for later alcohol misuse, especially when the injury is sustained in childhood. Previously, we modeled this pattern in mice, wherein females injured at postnatal day 21 drank significantly more than uninjured females, while we did not see this effect in males. However, the biological underpinnings of this sex difference have remained elusive. In this study, we utilize this preclinical model and traditional endocrine manipulations to assess the effect of perinatal sex steroids on post-injury ethanol response. We found that perinatal androgen administration and adult ovariectomy prevented the development of conditioned place preference to ethanol in females, while there was not an effect of gonadectomy either developmental time point on the severity of axonal degeneration. Finally, although TBI increased the number of microglia in males, there was no corresponding effect of gonadectomy, which suggests that males exhibit prolonged neuroinflammation after brain injury irrespective of circulating sex steroids. Taken together, our results indicate a potential role for ovarian sex steroids in the development of greater alcohol preference after a juvenile TBI in female mice.
中毒是导致受伤的主要风险因素，而创伤性脑损伤会增加日后酒精滥用的风险，尤其是在儿童期受伤时。此前，我们在小鼠中模拟了这种模式，其中在出生后第21天受伤的雌性小鼠比未受伤的雌性小鼠饮酒量明显更多，而在雄性小鼠中我们未观察到这种效应。然而，这种性别差异的生物学基础仍然难以捉摸。在本研究中，我们利用这种临床前模型和传统内分泌操作来评估围产期性类固醇对损伤后乙醇反应的影响。我们发现，围产期给予雄激素和成年后进行卵巢切除术可防止雌性小鼠对乙醇形成条件性位置偏好，而在任何发育时间点进行性腺切除术对轴突退变的严重程度均无影响。最后，尽管创伤性脑损伤增加了雄性小鼠中的小胶质细胞数量，但性腺切除术并无相应作用，这表明雄性小鼠在脑损伤后会出现持续的神经炎症，而与循环中的性类固醇无关。综上所述，我们的结果表明卵巢性类固醇在雌性小鼠幼年创伤性脑损伤后对酒精偏好增加的发展中可能起作用。
