Neuner Johanna, Filser Severin, Michalakis Stylianos, Biel Martin, Herms Jochen
Center for Neuropathology and Prion Research, Ludwig Maximilian University Munich, Feodor-Lynen-Straße 23, 81377 Munich, Germany.
German Center for Neurodegenerative Diseases (DZNE), Munich, Schillerstraße 44, 80336 Munich, Germany.
Sci Rep. 2014 Feb 3;4:3931. doi: 10.1038/srep03931.
Impaired olfaction is an early symptom in Parkinson disease (PD), although the exact cause is as yet unknown. Here, we investigated the link between PD-related mutant α-Synuclein (α-SYN) pathology and olfactory deficit, by examining the integration of adult-born neurons in the olfactory bulb (OB) of A30P α-SYN overexpressing mice. To this end, we chose to label one well-known vulnerable subpopulation of adult-born cells, the dopaminergic neurons. Using in vivo two-photon imaging, we followed the dynamic process of neuronal turnover in transgenic A30P α-SYN and wild-type mice over a period of 2.5 months. Our results reveal no difference in the number of cells that reach, and possibly integrate into, the glomerular layer in the OB. However, in mutant transgenic mice these new neurons have a significantly shortened survival, resulting in an overall reduction in the addition of neurons to the glomerular layer over time. We therefore propose unstable integration and impaired homeostasis of functional new neurons as a likely contributor to odour discrimination deficits in mutant α-SYN mice.
嗅觉减退是帕金森病（PD）的早期症状，尽管确切病因尚不清楚。在此，我们通过检查过表达A30P α-突触核蛋白（α-SYN）的小鼠嗅球（OB）中成年新生神经元的整合情况，研究了PD相关突变型α-SYN病理学与嗅觉缺陷之间的联系。为此，我们选择标记一个著名的成年新生细胞易损亚群，即多巴胺能神经元。利用体内双光子成像技术，我们在2.5个月的时间里跟踪了转基因A30P α-SYN和野生型小鼠神经元更替的动态过程。我们的结果显示，到达并可能整合到OB中肾小球层的细胞数量没有差异。然而，在突变转基因小鼠中，这些新神经元的存活时间显著缩短，导致随着时间的推移，肾小球层神经元的总体添加量减少。因此，我们认为功能性新神经元的整合不稳定和内环境稳态受损可能是突变型α-SYN小鼠气味辨别缺陷的一个原因。
