Journal of In Silico & In Vitro Pharmacology

Abstract

Neurodegenerative disorders are commonly associated with disruptions in motor and/or cognitive functions. Dementia is a common symptom of Parkinson disease and cellular accumulations of α[1]synuclein are a histological hallmark of that disorder. There are many animal models of Parkinson disease that utilize neurotoxins to destroy dopaminergic neurons that result in cognitive impairment but do not necessarily display α-synuclein accumulation. There are also transgenic models that broadly express human α-synuclein with resulting cognitive impairments. However, the differential effect of α[1]synuclein fibrils in specific brain structures on cognitive functions in rats has not been elucidated. In a pilot study, male Sprague-Dawley rats were injected bilaterally in the hippocampus and/or dorsal striatum with α-synuclein fibrils. Four to seven months later the animals were tested for cognitive function using novel object and novel place recognition paradigms. The results demonstrated a significant impairment of novel object recognition but not place recognition in rats injected in the dorsal striatum (P=0.01) and a trend toward impairment of novel place recognition but not object recognition in animals injected in the hippocampus (P=0.06). The results suggest that specific cognitive impairments in Parkinson disease may be related to the relative distribution of α-synuclein in cortical structure.