3-aminobenzamide, a Poly (adp-ribose) Polymerase Inhibitor, Restores Bioenergetics but Fails to Alleviate Excitotoxicity and Motor Functions in 3-nitropropionic Acid Intoxicated Mice
Year: 2015
Type: article
Abstract: Objective: The present study was undertaken to investigate the effects of 3-aminobenzamide (3-AB), a poly (ADP-ribose) polymerase 1 (PARP1) inhibitor, on motor functions along with brain excito toxicity and bioenergetics alterations in 3-nitropropionic acid (3-NPA) intoxicated mice model of Huntington’s disease (HD). Methods: Young healthy male C57BL/6J mice were pre-treated with vehicle/3-AB for a period of five days and intoxicated with two doses of 3-NPA (15 mg/kg, i. p) at 24 h interval on day 4 and 5. Animals were observed for motor functions 5 days after 3-NPA injection. They were sacrificed at the end of motor tests and brains were collected for neurochemical, bioenergetics, glial cells and cytokines analysis. Results: 3-AB treatment significantly increased the bioenergetics (ATP and NAD) and succinate dehydrogenase activity in 3-NPA intoxicated mice brains. But, it failed to decrease glutamate content, cytokines-TNFα and IL-1β and glial markers–glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA1) expressions. Further, 3-AB administered produced only a non-significant restoration of motor functions in 3-NPA intoxicated mice. Conclusion: The present study revealed that excito toxicity and inflammatory pathways are major perpetrators in 3-NPA induced neuro degeneration and motor dysfunction. Therapeutic approach with 3-AB alone may not be sufficient to manage the multi-cascade pathogenetic mechanisms in HD neither symptomatic management too.
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W1610311432