Department of Molecular Neurology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Department of Molecular Neurology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Neurobiol Aging. 2019 Aug;80:29-37. doi: 10.1016/j.neurobiolaging.2019.03.014. Epub 2019 Apr 1.
Axonal pathology precedes dopaminergic cell loss in Parkinson's disease (PD), indicating a dying back axonopathy of nigrostriatal projections. Although most attention focused on the dopaminergic system, increasing evidence implies a compromised serotonergic system in PD as well. By combining immunohistological and biochemical approaches, a profound layer-specific reduction of the serotonergic input to the prefrontal cortex (PFC) layers II and V/VI in aged mutant A53T α-synuclein-expressing mice (A53T mice) was detected. In addition, the altered fiber network was characterized by swollen axons and enlarged axonal varicosities within all PFC layers, but most pronounced in PFC layer I. Although prefrontal serotonin levels and synaptic protein expression were preserved, aged A53T mice showed increased levels of kinesin family member 1a and vesicular monoamine transporter 2. Together with increased tryptophan hydroxylase 2 mRNA levels in the raphe nuclei and an elevated serotonin receptor 1b expression in the PFC, these findings point to compensatory mechanisms within the serotonergic system to overcome the reduced neuritic input to the PFC in this transgenic animal model for PD.
在帕金森病（PD）中，轴突病变先于多巴胺能细胞丢失，表明黑质纹状体投射的退行性轴突病。尽管大多数注意力集中在多巴胺能系统上，但越来越多的证据表明 PD 中也存在 5-羟色胺能系统受损。通过结合免疫组织化学和生化方法，在老年突变 A53T α-突触核蛋白表达小鼠（A53T 小鼠）中检测到 5-羟色胺能传入到前额叶皮层（PFC）层 II 和 V/VI 的明显的层特异性减少。此外，改变的纤维网络的特征是在前额叶皮层的所有层中，都有轴突肿胀和轴突膨大增粗，但在 PFC 层 I 中最为明显。尽管前额叶皮层 5-羟色胺水平和突触蛋白表达保持不变，但老年 A53T 小鼠显示出驱动蛋白家族成员 1a 和囊泡单胺转运体 2 的水平增加。与中缝核中色氨酸羟化酶 2 mRNA 水平的升高和 PFC 中 5-羟色胺受体 1b 表达的升高一起，这些发现表明 5-羟色胺能系统中的代偿机制可克服该 PD 转基因动物模型中 PFC 中神经突传入的减少。
