Department of Neuroscience and Experimental Therapeutics, Texas A&M University School of Medicine, Bryan, TX 77807, USA.
Department of Biological Science, Texas A&M University, College Station, TX 77843, USA.
Int J Mol Sci. 2023 Nov 8;24(22):16084. doi: 10.3390/ijms242216084.
Traumatic brain injury (TBI) is a major health concern. Each year, over 50 million individuals worldwide suffer from TBI, and this leads to a number of acute and chronic health issues. These include affective and cognitive impairment, as well as an increased risk of alcohol and drug use. The dopaminergic system, a key component of reward circuitry, has been linked to alcohol and other substance use disorders, and previous research indicates that TBI can induce plasticity within this system. Understanding how TBI modifies the dopaminergic system may offer insights into the heightened substance use and reward-seeking behavior following TBI. The hippocampus, a critical component of the reward circuit, is responsible for encoding and integrating the spatial and salient aspects of rewarding stimuli. This study explored TBI-related changes in neuronal D2 receptor expression within the hippocampus, examining the hypothesis that sex differences exist in both baseline hippocampal D2 receptor expression and its response to TBI. Utilizing D2-expressing tdTomato transgenic male and female mice, we implemented either a sham injury or the lateral fluid percussion injury (FPI) model of TBI and subsequently performed a region-specific quantification of D2 expression in the hippocampus. The results show that male mice exhibit higher baseline hippocampal D2 expression compared to female mice. Additionally, there was a significant interaction effect between sex and injury on the expression of D2 in the hippocampus, particularly in regions of the dentate gyrus. Furthermore, TBI led to significant reductions in hippocampal D2 expression in male mice, while female mice remained mostly unaffected. These results suggest that hippocampal D2 expression varies between male and female mice, with the female dopaminergic system demonstrating less susceptibility to TBI-induced plasticity.
创伤性脑损伤（TBI）是一个主要的健康问题。每年，全世界有超过 5000 万人遭受 TBI，这导致了许多急性和慢性健康问题。这些问题包括情感和认知障碍，以及增加的酒精和药物使用风险。多巴胺能系统是奖励回路的关键组成部分，与酒精和其他物质使用障碍有关，先前的研究表明，TBI 可以诱导该系统的可塑性。了解 TBI 如何改变多巴胺能系统可能有助于深入了解 TBI 后物质使用和寻求奖励行为的增加。海马体是奖励回路的关键组成部分，负责编码和整合奖励刺激的空间和显著方面。本研究探讨了 TBI 相关的海马体神经元 D2 受体表达变化，检验了以下假设：即基线海马体 D2 受体表达及其对 TBI 的反应存在性别差异。利用表达 D2 的 tdTomato 转基因雄性和雌性小鼠，我们实施了假损伤或横向流体冲击损伤（FPI）TBI 模型，随后对海马体中 D2 表达进行了区域特异性定量。结果表明，雄性小鼠的海马体 D2 表达基线高于雌性小鼠。此外，性别和损伤对海马体 D2 表达的影响存在显著的交互作用，特别是在齿状回区域。此外，TBI 导致雄性小鼠海马体 D2 表达显著减少，而雌性小鼠基本不受影响。这些结果表明，海马体 D2 表达在雄性和雌性小鼠之间存在差异，雌性多巴胺能系统对 TBI 诱导的可塑性的敏感性较低。
