CHOLINERGIC TRANSMISSION IN THE BRAIN OF RATS WITH DIET INDUCED OBESITY (DIO)

The association between obesity and cognitive health is receiving increasing recognition. Obesity and its comorbidities are linked with impaired cognitive performance and neurodegenerative pathologies such as vascular dementia and Alzheimer’s disease (AD) in later life. High-fat diets (HFD) contribute to several of the key facets of AD: accumulation of β-amyloid, hyperphosphorylation of tau, and inflammation in the brain (including astrocyte and microglial activation). These neurodegenerative diseases affect the cholinergic system. This study evaluates the possible alterations of vesicular acetylcholine transporter (VAChT), of biosynthetic enzyme choline acetyltransferase (ChAT) and of acetylcholinesterase (AChE) in rats with diet-induced obesity (DIO) after 17 weeks of HFD (24 weeks of age), compared to the control rats with standard diet (CHOW). The obesity developed after 5 weeks of HFD (12 weeks of age). Body weight, systolic blood pressure, glycaemia and insulin levels were higher in DIO rats than in CHOW. No difference in total cholesterol and triglycerides was observed. In frontal cortex, hippocampus and brainstem, immunochemical and immunohistochemical techniques were performed to identify cholinergic markers. Our results showed a higher presence of VAChT and ChAT especially in frontal cortex and brainstem of obese rats. A reduced expression of VAChT was found in the frontal cortex of 24 weeks old DIO rats, while at the same age an increase of ChAT was evident in different brain areas. Based on our previous studies, in which were demonstrated astrogliosis and neurodegeneration in older DIO rats, the up-regulation in the synthesis of acetylcholine could be considered as a cholinergic recovery mechanism to overcome the brain injury.