Obesity-related to type-2 diabetes and brain cholinergic dysfunction: preliminary evidence from Obese Zucker Rats

Obesity is associated with glucose intolerance, type 2 diabetes, and dyslipidemia. Type-1 and type-2 diabetes are related with reduced performance on cognitive function likely depending by changes of the cholinergic system. The obese Zucker rats(OZRs), with leptin receptors mutation, represent a model of obesity related to type-2 diabetes. This study has investigated cholinergic system of OZRs compared with non-obese cohort lean Zucker rats(LZRs) to assess possible relationships between obesity and brain disorder. Male OZRs and LZRs of 16 weeks of age were used. Behavioural tests were performed to identify cognitive changes. Body weight, blood pressure and blood parameters were checked. The brain was processed for immunochemical and immunohistochemical analysis of neuronal specific nuclear protein (Neu-N), vesicular acetylcholine transporter (VAChT) and nicotinic(nAChR7) were also evaluated. OZRs of different ages, showed body weight, systolic pressure, glycemia, insulin, triglycerides and cholesterol levels higher in comparison with LZRs. Behavioural tests revealed in OZRs non changes in anxiety and emotional learning tasks. In frontal cortex, morphological and immunochemical analysis revealed a decrease of Neu-N in OZRs compared to LZRs. In OZRs, a decrease of VAChT and nAChR7 immunoreaction was observed. These results may represent the first step to characterize neurological and cholinergic changes potentially occurring in brain of obese rats. This preclinical evidence may be useful to clarify the pathophysiology of brain damage reported in obese individuals. Key words: Obesity, type-2 diabetes mellitus, brain cholinergic system