Departamento de Biología Celular and CIBER de Enfermedades Neurodegenerativas, Universidad de Valencia, E-46100 Burjassot, Spain.
Neurobiol Dis. 2010 Apr;38(1):92-103. doi: 10.1016/j.nbd.2010.01.003. Epub 2010 Jan 15.
Although generally considered a prototypical movement disorder, Parkinson's disease is commonly associated with a broad-spectrum of non-motor symptoms, including autonomic dysfunctions caused by significant alterations in catecholaminergic neurons of the peripheral sympathetic nervous system. Here we present evidence that alpha-synuclein is highly expressed by sympathetic ganglion neurons throughout embryonic and postnatal life and that it is found in tyrosine hydroxylase-positive sympathetic fibers innervating the heart of adult mice. However, mice deficient in alpha-synuclein do not exhibit any apparent alterations in sympathetic development. Sympathetic neurons isolated from mouse embryos and early postnatal mice are sensitive to the parkinsonian drug MPTP/MPP(+) and intoxication requires entry of the neurotoxin through the noradrenaline transporter. Furthermore, recovery of noradrenaline from cardiac sympathetic fibers is reduced in adult mice treated with MPTP systemically. However, MPP(+)-induced sympathetic neuron loss in vitro or MPTP-induced cardiac noradrenaline depletion in vivo is not modified in mice lacking alpha-synuclein. This is in clear contrast with the observation that dopaminergic neurons of the central nervous system are significantly less vulnerable to MPTP/MPP(+) in the absence of alpha-synuclein, suggesting different actions of this molecule in central and peripheral catecholaminergic neurons.
虽然通常被认为是一种典型的运动障碍，但帕金森病常伴有广泛的非运动症状，包括外周交感神经系统中儿茶酚胺能神经元显著改变引起的自主功能障碍。在这里，我们提供的证据表明，α-突触核蛋白在胚胎期和出生后整个生命过程中高度表达于交感神经节神经元，并且在支配成年小鼠心脏的酪氨酸羟化酶阳性交感神经纤维中发现了α-突触核蛋白。然而，缺乏α-突触核蛋白的小鼠在交感神经发育方面没有表现出任何明显的改变。从胚胎期小鼠和早期新生小鼠分离出的交感神经元对帕金森病药物 MPTP/MPP(+)敏感，并且神经毒素需要通过去甲肾上腺素转运体进入细胞才能发挥毒性作用。此外，系统给予 MPTP 处理的成年小鼠心脏交感神经纤维中的去甲肾上腺素回收减少。然而，体外 MPP(+)-诱导的交感神经元丢失或体内 MPTP 诱导的心脏去甲肾上腺素耗竭在缺乏α-突触核蛋白的小鼠中并未改变。这与中枢神经系统中的多巴胺能神经元在缺乏α-突触核蛋白时对 MPTP/MPP(+)的敏感性明显降低形成鲜明对比，这表明该分子在中枢和外周儿茶酚胺能神经元中的作用不同。
