Wagner Amy K, Chen Xiangbai, Kline Anthony E, Li Youming, Zafonte Ross D, Dixon C Edward
Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Exp Neurol. 2005 Oct;195(2):475-83. doi: 10.1016/j.expneurol.2005.06.009.
Dopamine (DA) systems are implicated in cognitive deficits following traumatic brain injury (TBI). Rodent studies have demonstrated that both environmental enrichment (EE) and sex hormones can influence DA systems. The dopamine transporter (DAT) plays a crucial role in regulating DA transmission, and previous work shows that DAT is decreased after TBI in males. Therefore, the purpose of this study was to examine the effects of gender and EE on frontal cortex and striatal DAT expression after TBI. Sprague-Dawley male (n = 24) and cycling female rats (n = 24) were placed into EE or standard housing after controlled cortical impact (2.7 mm, 4.0 m/s) injury or sham surgery (eight groups, n = 6/group). Four weeks post-surgery, bilateral frontal cortex and striatal DAT expression was examined via Western blot. Results demonstrated that there was a significant effect of injury, EE, and region on DAT expression (P < 0.05 all comparisons) on female groups. There were no significant DAT decreases in any region as a result of injury, however, EE did promote significant post-injury DAT decreases in the striatum and ipsilateral frontal cortex (P < 0.05 all comparisons) compared to female shams housed in the standard environment. For males, there was a significant effect of injury, EE, and region for male groups (P < 0.05 all comparisons). There were decreases in DAT expression in three regions studied for injured males housed in the standard environment compared to sham males in the standard environment (P < 0.05 all comparisons), however, EE did not add significantly to post-injury DAT decreases in these regions. These results suggest that CCI causes larger relative decreases in DAT expression for males compared to females and that treatment with EE has larger effects on post-injury DAT expression for females than males. These findings may have some relevance to treatment paradigms using dopaminergic neurostimulants after TBI.
多巴胺（DA）系统与创伤性脑损伤（TBI）后的认知缺陷有关。啮齿动物研究表明，环境富集（EE）和性激素均可影响DA系统。多巴胺转运体（DAT）在调节DA传递中起关键作用，先前的研究表明，雄性TBI后DAT会减少。因此，本研究的目的是探讨性别和EE对TBI后额叶皮质和纹状体DAT表达的影响。将Sprague-Dawley雄性大鼠（n = 24）和处于发情周期的雌性大鼠（n = 24）在控制性皮质撞击（2.7 mm，4.0 m/s）损伤或假手术后置于EE环境或标准饲养环境中（八组，每组n = 6）。术后四周，通过蛋白质免疫印迹法检测双侧额叶皮质和纹状体的DAT表达。结果表明，损伤、EE和脑区对雌性大鼠组的DAT表达有显著影响（所有比较P < 0.05）。损伤并未导致任何脑区的DAT显著降低，然而，与饲养于标准环境中的假手术雌性大鼠相比，EE确实促进了损伤后纹状体和同侧额叶皮质的DAT显著降低（所有比较P < 0.05）。对于雄性大鼠，损伤、EE和脑区对雄性大鼠组有显著影响（所有比较P < 0.05）。与饲养于标准环境中的假手术雄性大鼠相比，饲养于标准环境中的损伤雄性大鼠在研究的三个脑区中DAT表达均降低（所有比较P < 0.05），然而，EE并未显著增加这些脑区损伤后的DAT降低程度。这些结果表明，与雌性相比，控制性皮质撞击导致雄性大鼠DAT表达的相对降低幅度更大，并且EE治疗对损伤后雌性大鼠DAT表达的影响大于雄性。这些发现可能与TBI后使用多巴胺能神经兴奋剂的治疗模式有一定关联。
