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Agmatine mitigates behavioral abnormalities and neurochemical dysregulation associated with 3-Nitropropionic acid-induced Huntington's disease in rats.
- Source :
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Neurotoxicology [Neurotoxicology] 2024 May; Vol. 102, pp. 12-28. Date of Electronic Publication: 2024 Mar 06. - Publication Year :
- 2024
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Abstract
- Huntington'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 (10 mg/kg, i.p.) on days 1, 3, 5, 7, and 9 and then continued on agmatine treatment (5 - 20 µg/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, and TNF-α levels in discrete brain areas. Similarly, various agmatine modulators, which increase the endogenous agmatine levels in the brain, such as L-arginine (biosynthetic precursor), aminoguanidine (diamine oxidase inhibitor), and arcaine (agmatinase inhibitor) also demonstrated similar effects exhibiting the importance of endogenous agmatinergic pathway in the pathogenesis of 3-NP-induced HD like symptoms. The present study proposed the possible role of agmatine in the pathogenesis and treatment of HD associated motor incoordination, and psychiatric and cognitive complications.<br />Competing Interests: Declaration of Competing Interest Authors declare that there are no conflicts of any interest.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Male
Rats
Behavior, Animal drug effects
Brain drug effects
Brain metabolism
Rats, Wistar
Disease Models, Animal
Motor Activity drug effects
Rats, Sprague-Dawley
Neuroprotective Agents pharmacology
Nitro Compounds toxicity
Propionates toxicity
Agmatine pharmacology
Huntington Disease chemically induced
Huntington Disease metabolism
Huntington Disease drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9711
- Volume :
- 102
- Database :
- MEDLINE
- Journal :
- Neurotoxicology
- Publication Type :
- Academic Journal
- Accession number :
- 38453033
- Full Text :
- https://doi.org/10.1016/j.neuro.2024.03.002