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Nicotinamide reverses behavioral impairments and provides neuroprotection in 3˗nitropropionic acid induced animal model ofHuntington’s disease: implication of oxidative stress˗ poly(ADP˗ ribose) polymerase pathway

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Abstract

Huntington’s disease (HD) is characterized by cognitive and psychiatric impairment caused by neuronal degeneration in the brain. Several studies have supported the hypothesis that oxidative stress is the main pathogenic factor in HD. The current study aims to determine the possible neuroprotective effects of nicotinamide on 3-nitropropionic acid (3-NP) induced HD. Male Wistar albino rats were divided into six groups. Group I was the vehicle-treated control, group II received 3-NP (20 mg/kg, intraperitoneally (i.p.) for 4 days, group III received nicotinamide (500 mg/kg, i.p.). The remaining groups received a combination of 3-NP plus nicotinamide 100, 300 or 500 mg/kg, i.p. respectively for 8 days. Afterward, the motor function and hind paw activity in the limb withdrawal were tested; rats were then euthanized for biochemical and histopathological analyses. Treatment of rats with 3-NP altered the motor function, elevated oxidative stress and caused significant histopathological changes in the brain. The treatment of rats with nicotinamide (100, 300 and 500 mg/kg) improved the motor function tested by locomotor activity test, movement analysis, and limb withdrawal test, which was associated with decreased oxidative stress markers (malondialdehyde, nitrites) and increased antioxidant enzyme (glutathione) levels. In addition, nicotinamide treatment decreased lactate dehydrogenase and prevented neuronal death in the striatal region. Our study, therefore, concludes that antioxidant drugs like nicotinamide might slow progression of clinical HD and may improve the motor functions in HD patients. To the best of our knowledge, this study is the first to explore the neuroprotective effects of nicotinamide on 3-NP-induced HD.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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  1. Akram Sidhu

    Present address: UQ Diamantina Institute, Centre for Kidney Disease Research, Translational Research Institute, The University of Queensland, Woolloongabba, QLD, 4102, Australia

Authors and Affiliations

  1. Neuropharmacology Division, Department of Pharmacology, I.S.F College of Pharmacy, Ferozepur Road, Ghal Kalan, Moga, Punjab, 142001, India

    Akram Sidhu, Harsimran Kaur, Deepak Bhateja, Saurabh Sharma & Satyanarayana S. V. Padi

  2. UQ Diamantina Institute, Centre for Kidney Disease Research, Translational Research Institute, The University of Queensland, Woolloongabba, QLD, 4102, Australia

    Vishal Diwan

  3. Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab, 141012, India

    Charan K. Singh

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  1. Akram Sidhu
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Sidhu, A., Diwan, V., Kaur, H. et al. Nicotinamide reverses behavioral impairments and provides neuroprotection in 3˗nitropropionic acid induced animal model ofHuntington’s disease: implication of oxidative stress˗ poly(ADP˗ ribose) polymerase pathway. Metab Brain Dis 33, 1911–1921 (2018). https://doi.org/10.1007/s11011-018-0297-0

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