Title : Unraveling the neuroprotective and neurotoxic effects of different forms of ?-synuclein in vascular dementia through behavioral studies in wistar rats
Abstract:
Vascular Dementia (VD) is a cognitive disorder caused by vascular brain damage, leading to memory impairment and anxiety. This study aims to investigate the role of different forms of α-synuclein (α-Syn) in modulating the effects of VD and explore potential therapeutic benefits. Fifty-six male Wistar rats underwent bilateral common carotid artery occlusion to induce VD. After a month of recovery, rats received intraperitoneal injections of various forms of α-Syn (fibrillary, monomeric, oligomeric, and mutant variants fibrillar A30P and fibrillar A53T) at a dose of 50 µg/rat. Behavioral assessments, including the open field test, elevated plus maze, Novel Object Recognition, and Barnes maze, were conducted. The elevated plus maze test indicated increased anxiety in the VD group (P<0.001), which was alleviated by treatment with native fibrillar, monomeric and fibrillar mutant A30P α-synuclein variants (P<0.001). In the Barnes maze memory phase, data revealed increased primary latency and errors in the VD group (P<0.001), while treatment with native fibrillar and monomeric α-synuclein variants reduced these measures (P<0.001). The Novel Object Recognition test showed a significant reduction in discrimination index for the VD group compared to controls (P<0.001), which improved with treatment using native fibrillar, monomeric and fibrillar mutant A30P α-synuclein variants (P<0.001). Histological analyses indicated that VD increased dead neurons in the hippocampus (P<0.001), but native fibrillar and mutant A30P α-synuclein variants reduced neuron death (P<0.001). Findings show that specific forms of α-synuclein, particularly fibrillary, and fibrillar A30P, may offer promising therapeutic strategies for alleviating cognitive deficits in VD.
Keywords: Vascular Dementia, Cognitive Dysfunction, Α-Synuclein
