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Tarasova TV, Lytkina OA, Goloborshcheva VV, Skuratovskaya LN, Antohin AI, Ovchinnikov RK, Kukharsky MS.2018. Genetic inactivation of alpha-synuclein affects embryonic development of dopaminergic neurons of the substantia nigra, but not the ventral tegmental area, in mouse brain. PeerJ Preprints6:e26547v2https://doi.org/10.7287/peerj.preprints.26547v2
Lesion of the dopaminergic neurons of the nigrostriatal system is a key feature of Parkinson's disease (PD). Alpha-synuclein is a protein that is a major component of Lewy bodies, histopathological hallmarks of PD, and is involved in regulation of dopamine (DA) neurotransmission. Previous studies of knockout mice have shown that inactivation of alpha-synuclein gene can lead to the reduction in number of DA neurons in the substantia nigra (SN). DA neurons of the SN are known to be the most affected in PD patients whereas DA neurons of neighboring ventral tegmental area (VTA) are much less susceptible to degeneration. Here we have studied the dynamics of changes in TH-positive cell numbers in the SN and VTA during a critical period of their embryonic development in alpha-synuclein knockout mice. This precise study of DA neurons during development of the SN revealed that not only is the number of DA neurons reduced by the end of the period of ontogenic selection, but that the way these neurons are formed is altered in alpha-synuclein knockout mice. At the same time, DA neurons in the VTA are not affected. Alpha-synuclein exerts a modulating effect on the formation of DA neurons in the SN and has no effect on the formation of DA neurons in VTA, the structure that is much less susceptible to degeneration in PD brain, suggesting a potential role of alpha-synuclein in the development of the population of DA neurons in substantia nigra.
Numbers of typos were corrected and figure 2 were changed according to reviewer's suggestions.
Raw data for the number of TH-positive neurons in SN of alpha-synuclein knockout and control WT mice in embryogenesis and number of TH-positive neurons in SN and VTA on E13.5 day