Assessing the Neuroprotective Effects of Docosahexaenoic Acid in 6‐Hydroxydopamine Induced Parkinsonism in Rats

Abstract

Parkinson's Disease (PD) is the second most common neurodegenerative disease throughout the United States. Dopamine (DA) Replacement Therapy is the standard treatment for the motor symptoms of PD. However, there is growing interest in studying newer therapeutic compounds. Polyunsaturated omega‐3 fatty acids have been associated with neuroprotective roles. In this study, we aimed to investigate the neuroprotective effects of Docosahexaenoic Acid (DHA) in 6‐Hydroxydopamine (6‐OH‐DA) unilaterally lesioned rats. Behavioral assays were conducted for the assessment of locomotor activity, stride length and limb asymmetry. Neurochemical analysis of DA levels and its major metabolite DOPAC in the striatum was performed using high performance liquid chromatography (HPLC‐ED). Biochemical estimation of oxidative stress markers like Glutathione and Reactive Oxygen Species (ROS) was conducted. Semiquantitative measurements of total Tyrosine Hydroxylase (TH) and Phospho‐TH (Ser 40) in striatal homogenates were assessed using Western Blot analysis. Our results demonstrate that DHA significantly improved stride length and limb asymmetry in the parkinsonian rats. No significant improvement was observed in locomotor activity. DHA significantly improved dopamine levels in the lesioned striatum along with a significant decrease in oxidative stress markers. There was a significant increase in expression of total Tyrosine Hydroxylase (TH) and Phospho‐TH (Ser 40) with DHA treatment. In conclusion, DHA protected the dopaminergic neurons and led to increased dopamine levels and improved motor function. We are currently studying the specific role and mechanism involved to establish a link between DHA mediated neuroprotection and increased levels of Tyrosine Hydroxylase. These results support targeting free fatty acid systems for the development of new therapeutics for PD.Support or Funding InformationStudies were supported by the National Institute of Neurological Disorders and Stroke, a component of the National Institutes of Health, by grant number NS095239. Moniri N – Principal Investigator; Murnane KS – Co‐InvestigatorThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.