Astrogliosis in the brain of obese Zucker rat: a model of metabolic syndrome

Abstract

Metabolic syndrome (MetS) is a disorder characterized primarily by the development of insulin resistance. Insulin resistance and subsequent hyperinsulinemia, originating from abdominal obesity, increases the risk of cerebrovascular and cardiovascular disease and all-cause mortality. Obesity is probably a risk factor for Alzheimer's disease and vascular dementia and is associated with impaired cognitive function. The obese Zucker rat (OZR) represents a model of type 2 diabetes exhibiting a moderate degree of arterial hypertension and of increased oxidative stress. To clarify the possible relationships between MetS and brain damage, the present study has investigated brain microanatomy in OZRs compared with their littermate controls lean Zucker rats (LZRs). Male OZRs and LZRs of 12 weeks of age were used. Their brain was processed for immunochemical and immunohistochemical analysis of glial fibrillary acidic protein (GFAP). In frontal and parietal cortex of OZRs a significant increase in the number of GFAP immunoreactive astrocytes was observed. Similar findings were found in the hippocampus, where an increased number of GFAP immunoreactive astrocytes were detected in the CA1 and CA3 subfields and dentate gyrus of OZRs compared to the LZRs. These findings indicating the occurrence of brain injury accompanied by astrogliosis in OZRs suggest that these rats, developed as an animal model of type 2 diabetes, may also represent a model for assessing the influence of MetS on brain. The identification of neurodegenerative changes in OZRs may represent the first step for better characterizing neuronal involvement in this model of MetS and possible treatment for countering it.