Objective: Our aim was to characterize the progression of microglial activation during disease progression in a transgenic mouse model of multiple system atrophy (MSA).

Background: Microglial cells have been demonstrated to play a pivotal role in MSA pathogenesis, in particular in the neuroinflammatory processes involved in the disease progression. Furthermore, it has become clear that the way microglia act in this context cannot be defined as entirely positive or detrimental, as they show both sides of the coin, and are therefore extremely interesting actors during the disease development.

Methods: For the analysis we used transgenic mice overexpressing α-synuclein in oligodendrocytes under the proteolipid protein promoter (MSA mice) and wild type controls at the age of two, five and fifteen months. We performed morphological characterization of microglia during stereological analysis of different brain areas which are relevant to MSA, according to a rating scale developed by Sanchez-Guajardo et al. (2010). This scale allows the subdivision of microglia in four different forms (A, B, C and D), characterized by increasing levels of activation (from resting microglia to completely activated). We also used a ProcartaPlex Multiplex immunoassay to measure cytokine and chemokine levels in the brain and plasma of the same experimental groups. Two-way ANOVA with variables age and genotype was used for the statistical analysis.

Results: Preliminary data show an increased presence of activated microglia in older MSA mice as compared to both younger MSA mice and control animals of the same age. Furthermore, the levels of specific cytokines and chemokines in the brain change significantly with ageing in MSA mice in contrast to healthy controls and may contribute to the pathogenesis of the disease.

Conclusions: Our findings suggest that there is an increase in the neuroiflammatory state in MSA mice that parallels the progression of the disease. The results of this study will serve future identification of therapeutic targets related to neuroinflammation in MSA. Acknowledgement: This study was supported by grants of the Austrian Science Fund (FWF) W1206-08, P25161 and F4414.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/progression-of-microglial-activation-and-neuroinflammatory-responses-in-a-transgenic-mouse-model-of-multiple-system-atrophy/