Effect of N-Acetyl Cysteine on Intracerebroventricular Colchicine Induced Cognitive Deficits, Beta Amyloid Pathology, and Glial Cells

Among the many factors responsible for the cognitive decline in Alzheimer's disease, beta amyloid protein and plaque formation is crucial. This amyloid pathology is associated with activation of glial cells and oxidative stress but whether oxidative stress activates beta amyloid protein in the neurons is not clear. Further the expression of microglia is also known to vary during pathogenesis of beta amyloid plaques. The aim of the present study is to evaluate the antioxidant effect of NAC on amyloid pathology and cognition and also to investigate the link between amyloid pathology and glial cells activation. Intracerebroventricular colchicine in rats known mimics human AD in many aspects including memory loss, oxidative stress, and hyper phosphorylation of tau protein. The animal groups consisted of age matched control, sham operated, AD, and NAC treated in AD models of rats. Cognitive function was evaluated in active avoidance test; beta amyloid protein, beta amyloid plaques, astrocytes, and microglia cells were quantified using immunohistochemistry in hippocampal and prefrontal cortices. Colchicine has resulted in significant cognitive loss, increased intraneuronal beta amyloid protein expression, increased reactive astrocytes, and activated microglia in all the regions of the hippocampus and prefrontal cortices. The antioxidant NAC has reversed the cognitive deficits and inhibited microglia activation but failed to inhibit BAP expression and astrocytosis. Intraneuronal BAP accumulation is deleterious and known to adversely affect cognition, but in this study in spite of intraneuronal BAP accumulation, the cognition is restored. It can be postulated that NAC might have reversed the effect of intraneuronal beta amyloid protein by acting on some downstream compensatory mechanisms which needs to be explored.