Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Cell Biochem Biophys. 2011 Jan;59(1):49-56. doi: 10.1007/s12013-010-9110-3.
In order to examine the acute effects of L: -DOPA treatment following 6-hydroxydopamine (6-OHDA) injection into rat medial forebrain bundle (MFB). Sprague-Dawley rats (n = 48) received either 6-OHDA, via intracranial unilateral injection, into the MFB (experimental group) or saline 0.9% (control group). Administration of L: -DOPA or saline 0.9% began 1 month after the 6-OHDA injection for 10 consecutive days. Within 3 days, an increase in the density of striatal tyrosine hydroxylase (TH) immunoreactive fibers within the striatum, when compared to the control group was observed. There was no difference in the loss of substantia nigra pars compacta (SNpc) dopaminergic (DA) neurons between. The greater density of TH fibers in the striatum following L: -DOPA may be related to recovery of the DA phenotype and/or sprouting of TH axon terminals. Only animals with severe cell loss in the SNpc experienced abnormal involuntary movements (AIMs) or "dyskinesias" in response to L: -DOPA, which did not correlate with striatal TH fiber density, suggesting that induction of TH-positive fibers does not contribute to the occurrence of dyskinesia. The relationship between cell loss, fiber density and AIM to the abundance of markers of microglial activation were also examined. Iba-1, a microglial marker, immunoreactivity was not affected by L: -DOPA treatment, was not correlated with the severity of AIM indicating that microglial activation does not contribute to dyskinetic phenomena.
为了研究左旋多巴（L: -DOPA）治疗 6-羟多巴胺（6-OHDA）注入大鼠中脑边缘束（MFB）后的急性影响。Sprague-Dawley 大鼠（n = 48）通过颅内单侧注射 6-OHDA 进入 MFB（实验组）或生理盐水 0.9%（对照组）。6-OHDA 注射后 1 个月开始连续 10 天给予 L: -DOPA 或生理盐水 0.9%。与对照组相比，在 3 天内观察到纹状体中纹状体酪氨酸羟化酶（TH）免疫反应纤维的密度增加。两组间黑质致密部（SNpc）多巴胺能（DA）神经元的丢失无差异。L: -DOPA 后纹状体中 TH 纤维密度的增加可能与 DA 表型的恢复和/或 TH 轴突末梢的发芽有关。只有 SNpc 中细胞丢失严重的动物在接受 L: -DOPA 后出现异常不自主运动（AIM）或“运动障碍”，与纹状体 TH 纤维密度无关，表明诱导 TH 阳性纤维不会导致运动障碍的发生。还研究了细胞丢失、纤维密度与 AIM 与小胶质细胞激活标志物丰度之间的关系。小胶质细胞标志物 Iba-1 的免疫反应性不受 L: -DOPA 治疗的影响，与 AIM 的严重程度无关，表明小胶质细胞激活不参与运动障碍现象。
