Temporal profile of the development of cellular hallmarks of Parkinson’s disease following repeated mild traumatic brain injury (22056)
Repeated mild traumatic brain injury (rmTBI) is prevalent in contact sports and increases risk of developing neurodegenerative conditions including Alzheimer’s and Parkinson’s disease (PD). However, definitive links have not been established between primary injury and cellular hallmarks of neurodegenerative disease. While the significance of alpha synuclein (α-syn), tau protein and neuroinflammation in secondary neurodegeneration is widely acknowledged, the onset and progression of these pathologies are unknown. Using a rat model of closed‑head rmTBI, where sham (no injury) or two injuries were delivered 24h apart, this project investigated increases in phosphorylated α-syn, tau, activated CD8+ T cells (Granzyme B+) and microglia density (Iba1+) in the brain in a temporal manner, with the goal of identifying the onset of each pathology and their relationships. Whole-brain sections collected at 4 days, 2 weeks, 3 months and 6 months post-injury were assessed by multiplexed fluorescence immunohistochemistry, imaged on a Zeiss AxioScan Z.1 Digital Slide Scanner and analysed using the Zeiss Zen Blue software. (Phosphorylated Tau, Phosphorylated alpha-synuclein, and Tyrosine Hydroxylase), was performed via multiplexed immunohistochemistry and whole slide scans were imaged using the Zeiss AxioScan Z.1 Digital Slide Scanner at CHIRI. Although analysis is ongoing, preliminary analysis indicates increased cytoplasmic accumulation of phosphorylated tau and alpha-synuclein in dopaminergic neurons (Tyrosine Hydroxylase+) in the substantia nigra, a hallmark of PD. Increased numbers of activated CD8+ T cells was also observed. Data from this study will establish, for the first time, a biological link between rmTBI in young adulthood, neuroinflammation and neurodegenration later in life.