Sutherland, Rob

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    Effects of TCB-2 on Alzheimer's neuropathology
    (University of Lethbridge, Dept. of Neuroscience, 2022) Cocco, Giulia; Sutherland, Robert J.
    Background: In recent years there’s been a surging interest in the pharmacological benefits of serotonin receptor (5-HTR) agonists to treat psychiatric disorders, one of them being Alzheimer’s Disease (AD). Research has hinted at the effects of these 5-HTR agonists on hippocampal (HPC) neurogenesis, Amyloid-b (Ab) plaque deposition and microglial activation. These are all hallmark biomarkers of AD. In light of the rise in dementia diagnoses, studies should examine different methods to moderate these symptoms. Objective: This study shows the effects of the drug (4-Bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine hydrobromide (TCB-2) as a candidate to ameliorate AD biomarkers of neuropathology in the APPNL-G-F mouse model at 6 and 10 months of age (early and late stages). Methods: Fourteen APPNL-G-F mice were fed 0.35g of Nutella®. The treatment group received 5 mg/kg of TCB-2 whereas the controls received the vehicle only. Feeding occurred every 3 days for the length of 29 days. Afterward, they were tested on the Novel Object Recognition (NOR) task for 6 days and subsequently perfused to collect their brains and apply immunohistochemistry analysis. Results: The TCB-2 treatment was significantly more effective at decreasing A plaque count in the younger cohort, resulting in a trend of cognitive enhancement as well. It provided anti-inflammatory aid and decreased HPC surface area across all ages. Conclusion: Due to the ambiguous role of serotonin in learning and memory, our research hopes to expand its literature. The results prove that there’s potential for 5-HTR agonists to be used as medical treatments to prevent the development of AD neuropathology.