Cerebrovascular alterations and synaptic plasticity modulation in rats developing obesity

The systemic effects, such as increased fat mass, hypertension, insulin resistance and metabolic disorders, have been identified as factors that may lead to cognitive dysfunction. For these reasons obesity represents a risk factor for the development of cerebrovascular disease and cognitive decline. To investigate the possible relationships between obesity and nervous system changes, neuronal, glial and synaptic vesicular markers were studied in the brain of rat developing obesity (Diet-Induced Obesity DIO) after 17 weeks of hypercaloric diet compared to the control rats with not fat diet (CHOW). Food consumption, fat mass content, blood pressure and blood parameters were checked out. Behavioural tests were used to estimate cognitive performance, while RT-qPCR, immunochemical and immunohistochemical analysis were performed to evaluate modulation of specific cerebrovascular parameters. The obese phenotype starts to develop after 5 weeks of high fat diet exposure and body weight was higher in DIO rats compared to CHOW during the treatment. Systolic blood pressure, glycaemia and insulin were higher in DIO rats only after 17 weeks of high fat diet. No changes in total cholesterol and triglycerides were observed. Furthermore increase of thiobarbituric reactive substances and of oxidated proteins, was observed in the serum and brain of DIO rats compared to CHOW rats. The open-field test revealed, in the older DIO rats, a decrease of cumulative distance traveled, their number of rearings and increas-ing the total immobility time. In the passive avoidance test older DIO rats showed a reduc-tion of retention latency time, while the Morris Water maze revealed that rats performance (escape latency time, time spent for recognizing the position of the platform inside the pool the day of test) worsen in DIO rats compared to the CHOW rats. In the frontal cortex and hippocampus of older DIO rats compared to age-matched CHOW a reduction of neurofilament expression was revealed in the hippocampus of older DIO rats without decrease of the number of neurons. A modulation of acquaporin (AQP-4) and Glucose transport (GLUT-1), with an increased expression of the glial-fibrillary acid protein was found immunochemical and immunohistochemical analysis. A modulation of Transient Receptor Potential (TRP) channels and synaptic components was highlighted in cerebral areas of DIO rats after 17 weeks of high fat diet. Based on these data, obese rats developed astrogliosis, neurodegeneration, synaptic alterations possible related to impaired learning and memory tasks. Further studies are needed to better clarify the neuronal modifications and the implication of specific neurotransmitter systems in obesity