Lithium Chloride Rescues Dopaminergic Neurons in a Parkinson's Disease Rat Model Challenged with Rotenone.

Abstract

Introduction: Parkinson's disease, the second most common neurodegenerative disease, is still lacking an effective treatment that can stop dopaminergic cell loss in substantia nigra and alter disease progression.

Objective: The present study aimed to investigate the neuroprotective efficacy of lithium chloride in a rotenone-induced rat model of Parkinson's disease.

Methods: Forty male Sprague Dawley rats were assigned into 4 groups: control, rotenone-, rotenone and lithium chloride- and lithium chloride-treated groups. Rotenone (2 mg/kg b.w.) and lithium chloride (60 mg/kg b.w.) were, respectively, administered subcutaneously and orally five times a week for 5 weeks. At the end of each treatment, the neuroprotective efficacy of lithium chloride against rotenone-induced derangements was evaluated by some behavioral tests, biochemical analysis, gel electrophoresis, histopathology, and immunohistochemistry.

Results: Rotenone significantly resulted in neurobehavioral deficits, gastrointestinal dysfunction, decreased activities of catalase and superoxide dismutase, depleted glutathione, and increased levels of malondialdehyde. It also caused DNA fragmentation and loss of dopaminergic neurons in substantia nigra and decreased striatal tyrosine hydroxylase staining intensity. Concomitant treatment of rats with rotenone and lithium chloride significantly improved behavioral impairment and markedly alleviated gastrointestinal dysfunction. It also increased catalase activity and decreased malondialdehyde levels, indicating antioxidant effects. Moreover, it decreased DNA fragmentation, rescued dopaminergic neurons, and increased tyrosine hydroxylase immunoreactivity in the striatum compared to the rotenone-treated group.

Conclusion: Lithium chloride rescued dopaminergic neurons in a rotenone model of PD, possibly through the improvement of behavioral deficits, decreasing oxidative stress, and reducing DNA damage.