Scopolamine-induced greater alterations in neurochemical profile and increased oxidative stress demonstrated a better model of dementia: A comparative study

Cognitive decline is found to be a common feature of various neurological disorders like Alzheimer's disease (AD). In order to recapitulate AD associated cognitive deficits and to plan therapeutic strategies researchers have developed various preclinical dementia models to recapitulate different aspects of cognitive domains affected in AD brain. So, the present study was aimed to compare alterations in previously reported dementia models i.e. pharmacological (Scopolamine-induced and corticosterone-induced), Environmental (Aluminium-induced and noise-stress) and physiological (natural aging) models in rats in a single experimental study across three cognitive domains spatial, recognition, and associative memory and associated alterations in their oxidative status and neurochemical profile to select appropriate dementia model. All groups received their respective treatments for 14 days after which behavioural analysis was performed including Open Field test to assess ambulatory activity, Novel Object Recognition test, Morris Water Maze test and Passive Avoidance test for the assessment of recognition, spatial and associative memory. After monitoring the behavioural activities, rats were decapitated and their brains and hippocampus samples were collected for analysis of oxidative status and neurochemical profile. Results showed significant decline in different aspects of memory function in all dementia models which was more significant in scopolamine-injected rats. A significant decline in levels of monoamines and acetylcholine was also observed. In addition, significant alterations were also seen in oxidative profile indicating that cognitive decline could be associated with increased oxidative stress. Therefore, present findings highlight that for planning therapeutic strategies against cognitive dysfunctions, scopolamine-induced dementia model is the most appropriate dementia model to reveal AD-related cognitive impairment profile. (C) 2016 Elsevier Inc. All rights reserved.