• ALPHA-SYNUCLEIN
• MHCII
• Microglia
• Parkinson

Parkinson's disease is a neurodegenerative disease whose etiology is not completely defined yet. In fact, 90% of the cases are idiopathic, resulting from the interaction between genetic ad environmental factors. In this thesis, I focus on a particular polymorphism of CIITA gene (class II MHC transactivator) located on locus Vra4 on chromosome 10. The presence of this polymorphism is associated to lower levels of MHCII molecules on the surface of microglial cells in striatum: what I analyze in this thesis is if that can lead to an increased activation of the inflammatory response in CSN.
The study was carried on rat models belonging to two strains, DA and DA-vra4, which differ only because the latter expresses the polymorphism of Vra4; each of them was injected with either human alpha synuclein (simulating PD) or GFP (control group). After 12 weeks rats were sacrificed, their brain marked with Mac1, which binds specifically to microglia, and a stereological analysis of the cells was performed.
The level of activation of microglial cells is related to their shape, so that they can be divided into four groups, from A (resting cells) to D (more activated cells with phagocytic function). The group of DA-vra4 rats shows a significant increasing of C and D cells if compared to DA rats, where A and B cells outnumber. That means that DA-vra4 rats had a huge activation of microglia, and then major brain inflammation and damages.
That confirms the hypothesis of the important role of the polymorphism in Vra4 locus in modulating the immune response induced by the alpha synuclein aggregates typical of the disease, suggesting that it can be considered a genetic risk factor for PD.