Motor Dysfunction and Related Synaptic Organisation in AVV-Mediated Alpha-Synuclein Overexpression Model of Parkinson’s Disease

Year 2020, Volume: 40 Issue: 2, 74 - 82, 01.06.2020

Elif Çınar Gül Çakmaklı Banu Tel

Abstract

In Parkinson’s disease (PD), pathological intracellular aggregation of alpha-synuclein plays a key role in the neurodegenerative process. In this study, we aimed to investigate the progression of motor dysfunction and related changes in synaptic organization in an alpha-synuclein overexpressing viral vector model of Parkinson’s disease (PD) in rats.
Adeno-associated viral vectors (AAV) were stereotaxically injected bilaterally into substantia nigra (SN) together with dentate gyrus (DG). Further 7 animals were used as naïve controls. All animals were tested for locomotor activity for an hour from 3rd to 15th week. After that rats striati were analyzed by Western blotting for alpha-synuclein, tyrosine hydroxylase and synaptophysin expression.
Alpha-synuclein injected group moved less distance compare to control and their movement decreased by time till the 7th week then start to increase but yet slightly lower than the controls. Synaptophysin level was 13% and TH level was 25% decreased in alpha-synuclein group compare to controls.
Due to compensation mechanisms to protect neurons from neuronal death or alpha-synuclein accumulation in DG, alpha-synuclein group sustained to move in open field locomotor activity test. Although the model is open for improvement, it is useful to study early stage of PD and motor dysfunctions that occur due to alpha-synuclein overexpression.

Keywords

Parkinson’s disease, alpha-synuclein, locomotor activity, substantia nigra, dentate gyrus

Supporting Institution

Hacettepe Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi (BAP)

Project Number

ID:5291

Thanks

rAAV5-α-syn and rAAV5-eGFP viral vectors were kindly obtained from Michael J. Fox Foundation as a gift.

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