Center for Brain and Behavior Research, Division of Basic Biomedical Sciences, Sanford School of Medicine at the University of South Dakota, 414 East Clark St, Vermillion, SD, USA.
Center for Brain and Behavior Research, Department of Anatomy, University of Otago, PO Box 56, Dunedin 9054, New Zealand.
Neuroscience. 2023 Mar 15;514:38-55. doi: 10.1016/j.neuroscience.2023.01.034. Epub 2023 Feb 1.
Mild traumatic brain injuries (mild TBIs) can affect both males and females, but females are more likely to report long-term psychological complications, including changes in mood and generalized anxiety. Additionally, reproductive cycle phase has been shown to affect mild TBI symptom expression within females. These variances may result from sex differences in mild TBI-induced alterations to neurotransmission in brain regions that influence mood and emotion, possibly mediated by sex steroids. The hippocampus and amygdala are implicated in stress responses and anxiety, and within these regions, gamma-aminobutyric acid (GABA) and serotonin modulate output and behavioral expression. Metabolites of progesterone can allosterically enhance GABAergic signaling, and sex steroids are suggested to regulate the expression of the serotonin transporter (SERT). To determine how mild TBI might alter GABA receptor and SERT expression in males and females, immunocytochemistry was used to quantify expression of the alpha-1 subunit of the GABA receptor (α1-GABA), SERT, and a neuronal marker (NeuN) in the brains of adult male and naturally-cycling female rats, both with and without mild TBI, 17 days after injury. Mild TBI altered the expression of α1-GABA in the amygdala and hippocampus in both sexes, but the direction of change observed depended on sex and reproductive cycle phase. In contrast, mild TBI had little effect on SERT expression. However, SERT expression differed between sexes and varied with the cycle phase. These findings demonstrate that regulation of neurotransmission following mild TBI differs between males and females, with implications for behavioral outcomes and the efficacy of therapeutic strategies.
轻度创伤性脑损伤（mild TBIs）可影响男性和女性，但女性更有可能报告长期心理并发症，包括情绪和广泛性焦虑的变化。此外，已经表明生殖周期阶段会影响女性的轻度 TBI 症状表现。这些差异可能是由于轻度 TBI 引起的大脑中影响情绪和情感的神经递质传递的性别差异所致，这可能由性激素介导。海马体和杏仁核参与应激反应和焦虑，在这些区域内，γ-氨基丁酸（GABA）和 5-羟色胺调节输出和行为表达。孕酮的代谢物可以变构增强 GABA 能信号传递，并且性激素被认为调节 5-羟色胺转运体（SERT）的表达。为了确定轻度 TBI 如何改变男性和女性的 GABA 受体和 SERT 表达，使用免疫细胞化学技术来定量成年雄性和自然循环雌性大鼠的大脑中 GABA 受体的α1 亚基（α1-GABA）、SERT 和神经元标志物（NeuN）的表达，这些大鼠均患有轻度 TBI ，并在损伤后 17 天进行评估。轻度 TBI 改变了两性的杏仁核和海马体中的α1-GABA 表达，但观察到的变化方向取决于性别和生殖周期阶段。相比之下，轻度 TBI 对 SERT 表达的影响很小。然而，SERT 表达存在性别差异，并且随周期阶段而变化。这些发现表明，轻度 TBI 后神经传递的调节在男性和女性之间存在差异，这对行为结果和治疗策略的疗效有影响。
