Histopathological effect of high fat diet on substantia nigra pars compacta in rotenone-induced parkinson's type mouse model

Parkinson's disease (PD) is one of the common neurodegenerative diseases characterized by the loss of dopaminergic neurons located in the substantia nigra pars compacta (SNPc) area. Many studies have been conducted on mitochondrial dysfunction, oxidative stress and neuroinflammation to explain the neuronal death mechanisms involved in the pathogenesis of Parkinson's disease, but, although the processes are thought to cause Parkinson's disease, the reason is not fully understood. Since the cause is still unclear in most cases of Parkinson's disease, only symptomatic treatments such as pharmacotherapy, stereotactic neurosurgery and physiotherapy are available. Although these treatments reduce motor symptoms and improve the patient's quality of life, the clinical need for new treatments to prevent, stop or slow the progression of the disease is not fully understood. Furthermore, many studies now suggest an association between neurodegeneration and metabolic disorders. Long-term changes in diet have the potential to change the lipid composition of the brain. High fat diets (HFDs) are strongly associated with obesity and exert adverse effects on cognitive and behavioral functions. Epidemiological studies have shown that patients with obesity are at increased risk for neuropsychiatric disorders, including anxiety and depression. Agents used to induce neurodegeneration related to Parkinson's disease in rodents include rotenone. Rotenone is a pesticide that readily crosses the blood-brain barrier following systemic injection and inhibits complex I of the mitochondrial respiratory chain, inducing oxidative stress and subsequent pathology not limited to dopaminergic neurons. Rotenone is widely metabolized in vivo and the choice of route of exposure greatly influences the dose used. This model is based on the assumption that a high fat diet has an adverse effect. It was observed that rotenone substance caused loss of locomotor movement as in Parkinson's disease, and it was understood that the application of a high fat diet caused the exacerbation of these movements. Hematoxylin eosin, cresyl violet and silver staining were used to notice pathological findings, and as anticipated, intense pathological discoveries were observed in the PD+HFD group compared to the rotenone group. H-Scores were calculated in iNOS immunohistochemistry staining, and there are notable distinctions between the results of the PD+HFD and control groups (p<0.05). Ultimately, the apoptotic index was calculated with the TUNEL experiment, the highest values were acquired in the rotenone group and PD+HFD group, the second most increased in the HFD group, and the lowest in the control (p<0.05). As a result, in this study, high fat diet administration and duration caused a decrease in dopaminergic neurons in the substantia nigra pars compacta and increased the number of apoptotic neurons in a rotenone-induced Parkinson type mouse model.