Agmatine mitigates behavioral abnormalities and neurochemical dysregulation associated with 3-Nitropropionic acid-induced Huntington's disease in rats

Neurotoxicology. 2024 Mar 5:S0161-813X(24)00022-6. doi: 10.1016/j.neuro.2024.03.002. Online ahead of print.ABSTRACTHuntington's disease (HD) is a progressive neurodegenerative condition characterized by a severe motor incoordination, cognitive decline, and psychiatric complications. However, a definitive cure for this devastating disorder remains elusive. Agmatine, a biogenic amine, has gain attention for its reported neuromodulatory and neuroprotective properties. The present study was designed to examine the influence of agmatine on the behavioral, biochemical, and molecular aspects of HD in an animal model. A mitochondrial toxin, 3-nitro propionic acid (3-NP), was used to induce HD phenotype and similar symptoms such as motor incoordination, memory impairment, neuro-inflammation, and depressive-like behavior in rats. Rats were pre-treated with 3-NP (10mg/kg, i.p.) on days 1, 3, 5, 7, and 9 and then continued on agmatine treatment (5 - 20µg/rat, i.c.v.) from day-8 to day-27 of the treatment protocol. 3-NP-induced cognitive impairment was associated with declined in agmatine levels within prefrontal cortex, striatum, and hippocampus. Further, the 3-NP-treated rats showed an increase in IL-6 and TNF-α and a reduction in BDNF immunocontent within these brain areas. Agmatine treatment not only improved the 3-NP-induced motor incoordination, depression-like behavior, rota-rod performance, and learning and memory impairment but also normalized the GABA/glutamate, BDNF, IL-6, an...
Source: Neurotoxicology - Category: Neurology Authors: Source Type: research