Ameliorative Effects Of Vortioxetine In 3-Npa Induced Huntington\u27s Disease

Abstract

Huntington\u27s Disease (HD) is an autosomal dominant neurodegenerative disease caused by a mutation in the Huntingtin (HTT) gene. Clinically progressive motor dysfunction with cognitive decline, neuropsychiatric disorders like mood and behavioural abnormalities, and choreiform movements are its hallmarks. To lessen 3-nitropropionic acid (3-NPA)-induced HD-like pathology in a rodent model, this study sought to assess the neuroprotective pharmacological effects of vortioxetine, a primarily antidepressant drug that exhibits agonistic activity on the 5-HT1A receptor and antagonizes the serotonin transporter (SERT). The mitochondrial complex II inhibitor 3-NPA disrupts aerobic metabolism of cellular energy, induces oxidative stress, and causes neuronal damage like the pathophysiology of HD. To induce HD-like symptoms, 3-NPA (10 mg/kg intraperitoneally) was administered to male Wistar rats every other day for 28 days. Vortioxetine was subsequently administered orally at 5 and 10 mg/kg every day. Cognitive function was measured using the Morris Water Maze and Elevated Plus Maze, while the Rota rod test was used to measure motor coordination, and the Actophotometer was used to measure locomotor activity. Biochemical analyses measured striatal neurotransmitters, mitochondrial enzyme activity, and oxidative/nitrosative stress-related markers. Histopathological analysis of the cortex and hippocampal regions was performed to determine its impact on neuronal integrity. Vortioxetine treatment reduced oxidative stress, preserved the expression of mitochondrial electron transport complexes I, II, and IV, restored neurotransmitter equilibrium, and significantly ameliorated motor and cognitive deficits. Histopathology results showed a dose-dependent reduction in the evidence of neuronal degeneration, suggesting a neuroprotective effect. Thus, our findings suggest that Vortioxetine may exert its therapeutic effects in Huntington\u27s disease by improving mitochondrial function, reducing oxidative stress, and acting on the serotonin pathways. Thereby, vortioxetine, in addition to its known antidepressant properties, may emerge as possible treatment options in HD management. One might note limitations such as the need for validation in genetic HD models and long-term studies. Future studies should explore its therapeutic potential and molecular targets. The study emphasizes how Vortioxetine, including its role as a pharmacological agent, can be used for the treatment of neurodegenerative diseases, particularly in Huntington\u27s disease (HD), alleviating neuropsychiatric disorders. Additional clinical trials should determine the long-term safety and efficacy of vortioxetine for humans