Выявление альфа-синуклеина в обонятельных луковицах мыши в онтогенезе in vivo и в органотипической культуре

Abstract

Introduction. Alpha-synuclein (a-Syn) aggregation is considered as a cause of neurodegeneration in Parkinson’s disease. Accumulation and aggregation of a-Sin in olfactory bulbs (OB) presumably leads to olfactory impairment in parkinsonism However, the function of a-Syn and its localization in intact OB require requires more detailed research. The aim of the study was to characterize distribution of a-Syn in developing OB, and to assess the adequacy of OB explants cultivation as a model system for studying the pathogenesis of Parkinson disease. Materials and methods. Mice OB were studied on 17 and 19 embryonic days and in postanatal 2 and 7 days. Explants of OB on 17-th embryonic day and 2nd postnatal day were cultured for 24 hours in roller culture apparatus. Localization of a-Syn, synaptophysin and tyrosine hydroxylase were studied by immunohistochemical method. Results. Expression of a-Syn, synaptophysine and tyrosine hydroxylase was found in the peripheral layers of olfactory bulbs and changed under development, however, the localization of these proteins coincided only partially. On day 2 of postnatal development, a-Syn was detected in the bodies and processes of neurons in the mitral layer and in the olfactory glomeruli. At day 7, a-Syn was detected predominantly in the presynaptic endings in the olfactory glomeruli. In organotypic culture, the organization of OB corresponded to their native structure. Conclusions. In the developing OB α-Syn expression is associated with the formation of olfactory glomeruli and maturation of mitral layer cells. Distribution of α-Syn in intact OB consistent with the pattern of olfactory structures involvement in the neurodegenerative progression in Parkinson’s disease. Moreover we demonstrate the possibility of using organotypic OB cultures for modeling pathological processes in Parkinson disease. Key words: alpha-synuclein, olfactory bulbs, ontogenesis, organotypic culture.