Xu Xiupeng, Cao Shengwu, Chao Honglu, Liu Yinlong, Ji Jing
Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China; Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Environment & Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA.
Brain Res Bull. 2016 Jun;124:214-21. doi: 10.1016/j.brainresbull.2016.05.010. Epub 2016 May 19.
Several studies have demonstrated alterations in the dopamine (DA) system after traumatic brain injury (TBI). Additionally, the existence of significant sex-related differences in the dopaminergic system has long been recognized. Accordingly, the purpose of the present study was to investigate whether TBI would differentially alter, in female and male mice, the expression and the function of the striatal vesicular monoamine transporter-2 (VMAT-2), an important DA transporter. After controlled cortical impact (CCI) injury, female mice showed significantly lower striatal DA concentrations and K(+)-evoked DA output. By contrast, no significant sex-related differences were observed in the mRNA and protein levels of striatal dopamine transporter (DAT) and VMAT-2 and the methamphetamine (MA)-evoked DA output. These results demonstrated clear sex-related differences in striatal VMAT-2 function in response to TBI and suggested that female mice may be more sensitive to the TBI-induced inhibition of the VMAT-2 function, as indicated by the greater degree of deficits observed when the VMAT-2 DA-storage function was inhibited by TBI. Moreover, the TBI-induced suppression of locomotion was more pronounced than female mice. Such findings highlight the need for sex-specific considerations when examining differences among brain injury conditions.
多项研究表明，创伤性脑损伤（TBI）后多巴胺（DA）系统会发生改变。此外，多巴胺能系统中存在显著的性别差异这一点早已得到认可。因此，本研究的目的是调查TBI是否会对雌性和雄性小鼠纹状体囊泡单胺转运体2（VMAT - 2）这一重要的DA转运体的表达和功能产生不同的影响。在控制性皮质撞击（CCI）损伤后，雌性小鼠的纹状体DA浓度和钾离子诱发的DA释放量显著降低。相比之下，在纹状体多巴胺转运体（DAT）和VMAT - 2的mRNA和蛋白质水平以及甲基苯丙胺（MA）诱发的DA释放量方面，未观察到显著的性别差异。这些结果表明，在对TBI的反应中，纹状体VMAT - 2功能存在明显的性别差异，并且表明雌性小鼠可能对TBI诱导的VMAT - 2功能抑制更为敏感，这一点从TBI抑制VMAT - 2的DA储存功能时观察到的更大程度的缺陷中可以看出。此外，TBI诱导的运动抑制在雌性小鼠中比雄性小鼠更为明显。这些发现凸显了在研究脑损伤情况差异时考虑性别特异性的必要性。
