High fat diet feeding exacerbates the toxic effects of 6-hydroxydopamine in rats: Possible involvement of histone acetylation

Abstract

s / Parkinsonism and Related Disorders 22 (2016) e149ee192 e181 P 6.023. HIGH FAT DIET FEEDING EXACERBATES THE TOXIC EFFECTS OF 6HYDROXYDOPAMINE IN RATS: POSSIBLE INVOLVEMENT OF HISTONE ACETYLATION Sorabh Sharma, Rajeev Taliyan. Neuropharmacology Division, Department of Pharmacy, BITS-Pilani, Pilani, India Objectives: Clinical evidence has shown a correlation between Parkinson's disease (PD) and type 2 diabetes, as abnormal glucose tolerance has been reported in >50% of PD patients. Recently, insulin resistance was found to be present in 62% of PD patients with dementia, of whom 30% were glucose intolerant [1]. However, the underlying pathways are still elusive. Therefore, the present study was designed to explore the effect of insulin resistance on striatal dopaminergic neurons in an animal model of PD. Methods: High fat feeding in rodents is an established model of insulin resistance. We subjected rats to a normal pellet diet (NPD) or high-fat diet (HFD) for 8 weeks before infusing low dose of 6-hydroxydopamine (6OHDA) into the medial forebrain bundle. The animals were divided into four groups: 1) NPD 2) HFD 3) NPD + 6-OHDA 4) HFD + 6-OHDA. To delineate the molecular mechanisms, we study the changes in histone acetylation in striatum region. Results: The rats subjected to HFD exhibited characteristic features of insulin resistance. The animals treated with low dose 6-OHDA+ HFD feeding showed significant motor deficits as compared to HFD alone, NPD alone or NPD+ 6-OHDA treated animals. Moreover, these animals also exhibited greater dopamine depletion and significant reduction in histone acetylation as compared to other groups. Conclusions: The present study suggests that insulin resistance may lower the threshold for developing PD possibly via altering the epigenetic pathways such as histone acetylation.