关键词: &alpha, -突触核蛋白, A30P点突变, 神经发生, 嗅球

Abstract:

〗Abstract:Objective To investigate the influence of α-synuclein (SNCA) A30P point mutation in the neurogenesis in the olfactory bulb (OB) of adult mice，and to charify its effect in the pathogenesis of degenerative nervous diseases.Methods Normal C57BL mice,endogenous SNCA knockout mice (SNCA-/-) and SNCA knockout + human SNCA A30P knockin mice (A30P SNCA-/-) were used as experimental animals and were divided into C57BL,SNCA-/-, and A30P SNCA-/- groups.The coronal frozen sections of OB were made and the  morphological changes of  OB were  examined.Fluorescence immunohistochemistry of phosphohiston 3 (PH3),doublecortin (Dcx) and 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) staining were carried out to analyze the number of  PH3+ cells,the fluorescence intensity in Dcx+ neuroblasts and the cell densities after DAPI staining in OB.Results The cell densities in glomerular layer (GL) of OB of the mice in SNCA-/- and A30P SNCA-/- groups were decreased slightly.A slight deformation of OB morphology also occurred in A30P SNCA-/- group and the number of PH3+ cells in A30P SNCA-/- group  was decreased significantly compared with C57BL and SNCA-/- groups (P<0.05);the fluorescence intensities of Dcx+ neuroblasts in OB in SNCA-/- and A30P SNCA-/- groups were increased slightly and no evident changes of the cell densities in OB after DAPI staining was observed.Conclusion Human SNCA A30P point mutation can decrease the neuron proliferation in OB of the adult mouse brain,which suggests it play a certain inhibitory effect on the neurogenesis in adult OB.

Key words: &alpha, -synuclein, A30P point mutation, neurogenesis, olfactory bulb