Untitled

Abstract

Parkinson's disease has been a challenging neurodegenerative disorder for researchers and clinicians alike for decades. Though L-dopa has changed the management of PD to a considerable extent, effective solutions remain elusive since L-dopa, after a few years, partly loses its efficacy and develops dyskinesias as a complication, incapacitating the patient. Also, existing PD animal models using MPTP, rotenone, paraquet, etc cause significant suffering to the animals and also require a minimum of 22-25 days for induction. Hence, a better PD animal model was conceived considering the synergistic oxidative stress lipids, and rotenone induce on striatal neurons. The experiment compared the existing rotenone induction with combined rotenone and high-fat diet induction, carefully watching for motor and behavioural symptoms of PD in the Wistar rats in addition to measuring the biochemical profiles for toxicity, strictly following the ARRIVE guidelines for animal research. This study found that using HFD+Rot for induction not only shortened the duration of induction to a mean of 14 days but also reduced the suffering by reducing the number of intraperitoneal injections needed without significant derangement of safety biochemical parameters. This study also proves the effectiveness by demonstrating the reduced dopamine, serotonin levels in striatal neurons and increased oxidative stress parameters. To the best of our knowledge, no animal study shows a better PD model with all the neurobehavioural and biochemical features of PD with less time for induction. This new HFD+Rot model can therefore be employed to test therapeutics and neurobehavioural studies.