Neuroinflammation associated with non-motor symptoms in Parkinson’s disease- insights from the A53T mouse model

Abstract

The molecular mechanisms behind non-motor symptoms of Parkinson’s disease are poorly understood. In literature, the connection between neuroinflammation and depressive symptoms was observed in PD patients, however the implications of such findings are limited due to cerebrospinal fluid and blood derivates being the only obtainable samples for analysis. The aim of this preliminary study was to assess neuroinflammation, memory deficits and depression like symptoms associated with PD and to detect related proinflammatory mediators using a transgenic A53T mouse model. The transgene consists of the human α-synuclein sequence with the A53T mutation driven by the mouse prion protein (PrP) promoter resulting in overexpression of human α-synuclein in key structures associated with PD. Although it was determined that microglial activation is increased in these mice, the specific cytokine profile driving the inflammation has not been characterized in literature. We have examined the expression of three key inflammatory mediators (tumor necrosis factor alpha (TNFα), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) described as markers associated with the microglial pro-inflammatory phenotype in the prefrontal cortex, hippocampus, and striatum of 8 male 6 months old A53T mice. Additionally, depressive like symptoms and anhedonia were assessed using Tail Suspension Test and Sucrose Preference Test respectively, while cognitive status and memory deficits were assessed using Novel Object Recognition Test. Non-transgenic littermates were used as controls. Obtained results depict a characteristic behavioral and pro-inflammatory profile in the transgenic animals. The implications of the obtained findings and the potential for using the A53T model as a tool for studying non-motor features of PD are further discussed.