OBESITY-RELATED CEREBROVASCULAR INJURY IN OBESE ZUCKER RATS

Increased food intake, reduced physical activity and altered metabolic processes are variables affecting energy balance and inducing obesity. Obesity is becoming in the industrialized countries a relevant medical challenge being associated with the development of chronic diseases affecting also nervous system. Metabolic syndrome (MetS), defined by a constellation of an interconnected physiological, biochemical, and metabolic factors is directly correlated to obesity. It increases the risk of atherosclerotic cardiovascular disease, type 2 diabetes mellitus (T2DM) and all cause mortality. The obese Zucker rats (OZRs), with a mutation in leptin receptor, represent a model of obesity exhibiting T2DM with a moderate degree of arterial hypertension. OZRs are characterized by the simultaneous occurrence of hyperglycaemia, hyperinsulinaemia and hyperlipidaemia. The aim of this work was to characterize brain microanatomy of OZRs compared to their non-obese cohort lean Zucker rats (LZRs) to assess possible cerebrovascular injury related to obesity. Male OZRs and LZRs of 12, 16 and 20 weeks of age were used. Body weight, blood pressure and blood parameters were checked in different groups. Neuronal, glial and blood-brain-barrier changes were assessed by immunochemical and immunohistochemical techniques. In frontal cortex and hippocampus a decrease of neuronal specific nuclear protein positive cells in older OZRs group compared to age matched LZRs was noticeable. These changes were accompanied with a reduced neurofilament immunoreaction without changes of the dendritic protein MAP-2. In OZRs an increased expression of glial fibrillary acidic protein immunoreactive astrocytes was observed compared to LZRs. Blood brain barrier of older OZRs revealed an increased expression of aquaporin-4 and glucose transporter-1 compared to LZRs. These data suggest that OZRs developed a specific neuronal, glial and cerebrovascular changes further suggesting that OZRs may represent an useful animal model for assessing the influence of obesity/MetS on the brain. This could contribute to clarify the pathophysiology of nervous system damage reported in obese individuals and/or affected by MetS and to identify possible treatment strategies.