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

Abstract

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.

Effect of sacubitril/valsartan on cognitive impairment in colchicine‐induced Alzheimer's model in rats

“…*P < 0.05 versus normal control, #P < 0.05 versus untreated AD rats, €P < 0.05 versus sacubitril/ valsartan-treated rats inducing oxidative stress, microtubule disruption, cholinergic system dysfunction, and increasing the expression of beta amyloid protein. This results in abnormal accumulation of Aβ peptide in brain [21]. In accordance with previous studies [18,21,39], icv injection of colchicine in the untreated AD group increased escape RLs across learning days and decreased time spent in target quadrant in MWM test.…”

“…This results in abnormal accumulation of Aβ peptide in brain [21]. In accordance with previous studies [18,21,39], icv injection of colchicine in the untreated AD group increased escape RLs across learning days and decreased time spent in target quadrant in MWM test. In addition, it lowered RL in passive avoidance task.…”

“…was given to rats in order to prevent sepsis. Special care was conducted until spontaneous movement occurred [21].…”

N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks)

“…Animal studies have shown significant promise improving cognitive function even though beta-amyloid pathology was unchanged [ 113 ]. There is some evidence that NAC as an adjuvant may slow the progression of dementia; however, this effect was seen clinically in a nutraceutical containing several ingredients including NAC [ 114 ].…”

Effect of resveratrol and combination of resveratrol and donepezil on the expression of microglial cells and astrocytes in Wistar albino rats of colchicine-induced Alzheimer’s disease

“…5 ) and astrocytes (Fig. 6 ) were done according to the protocol of Streit ( 1990 ) and Joy et al ( 2019 ). The quantitative analysis was done under light microscopy (20X).…”