1,4-dihydroxy-2-naphthoic acid prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced motor function deficits.

Autor:	Madison CA; Behavioral and Cellular Neuroscience, Department of Psychological and Brain Sciences., Debler RA; Behavioral and Cellular Neuroscience, Department of Psychological and Brain Sciences., Gallegos PL; Behavioral and Cellular Neuroscience, Department of Psychological and Brain Sciences., Hillbrick L; Behavioral and Cellular Neuroscience, Department of Psychological and Brain Sciences., Chapkin RS; Departments of Nutrition., Safe S; Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas, USA., Eitan S; Behavioral and Cellular Neuroscience, Department of Psychological and Brain Sciences.
Jazyk:	angličtina
Zdroj:	Behavioural pharmacology [Behav Pharmacol] 2025 Feb 01; Vol. 36 (1), pp. 40-46. Date of Electronic Publication: 2024 Dec 12.
DOI:	10.1097/FBP.0000000000000806
Abstrakt:	Parkinson's disease (PD), characterized by death of dopaminergic neurons in the substantia nigra, is the second most prevalent progressive neurodegenerative disease. However, the etiology of PD is largely elusive. This study employed the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rodent model to examine the effectiveness of 1,4-dihydroxy-2-naphthoic acid (1,4-DHNA), an aryl hydrocarbon receptor (AhR) active gut bacteria-derived metabolite, in mitigating MPTP's motoric deficits, and the role of AhR in mediating these effects. Male C57BL/6 mice were fed daily with vehicle, 20 mg/kg 1,4-DHNA, or AhR-inactive isomer 3,7-DHNA, for 3 weeks before administration of 80 mg/kg MPTP or vehicle. Four weeks later, mice were assessed for motoric functions. Both 1,4-DHNA and 3,7-DHNA prevented MPTP-induced deficits in the motor pole test and in the adhesive strip removal test. Additionally, 1,4-DHNA improved balance beam performance and completely prevented MPTP-induced reduction in stride length. In contrast, 3,7-DHNA, an AhR-inactive compound, did not improve balance beam performance and had only a partial effect on stride length. This study suggests that natural metabolites of gut microbiota, such as 1,4-DHNA, could be beneficial to counteract the development of motor deficits observed in PD. Thus, this study further supports the hypothesis that pathological and mitigating processes in the gut could play an essential role in PD development. Moreover, this indicates that 1,4-DHNA's ability to combat various motor deficits is likely mediated via multiple underlying molecular mechanisms. Specifically, AhR is involved, at least partially, in control of gait and bradykinesia, but it likely does not mediate the effects on fine motor skills. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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