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Targeting Neuroinflammation with Abscisic Acid Reduces Pain Sensitivity in Females and Hyperactivity in Males of an ADHD Mice Model
Insitute of Advanced Materials (INAM), University of Jaume I ; Faculty of Health Sciences, University of Jaume I (ESP).
Faculty of Health Sciences, University of Jaume I (ESP).ORCID iD: 0000-0002-9759-1665
Marc Landry, University of Bordeaux, Bordeaux (FRA).ORCID iD: 0000-0003-3936-324X
University West, Department of Health Sciences, Section for health promotion and care sciences. (LOVHH)ORCID iD: 0000-0002-8854-0399
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2023 (English)In: Cells, E-ISSN 2073-4409, Vol. 12, no 3, p. 465-486Article in journal (Refereed) Published
Abstract [en]

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental syndrome characterized by dopaminergic dysfunction. In this study, we aimed to demonstrate that there is a link between dopaminergic deficit and neuroinflammation that underlies ADHD symptoms. We used a validated ADHD mice model involving perinatal 6-OHDA lesions. The animals received abscisic acid (ABA), an anti-inflammatory phytohormone, at a concentration of 20 mg/L (drinking water) for one month. We tested a battery of behavior tests, learning and memory, anxiety, social interactions, and pain thresholds in female and male mice (control and lesioned, with or without ABA treatment). Postmortem, we analyzed microglia morphology and Ape1 expression in specific brain areas related to the descending pain inhibitory pathway. In females, the dopaminergic deficit increased pain sensitivity but not hyperactivity. In contrast, males displayed hyperactivity but showed no increased pain sensitivity. In females, pain sensitivity was associated with inflammatory microglia and lower Ape1 levels in the anterior cingulate cortex (ACC) and posterior insula cortex (IC). In addition, ABA treatment alleviated pain sensitivity concomitant with reduced inflammation and normalized APE1. In males, ABA reduced hyperactivity but had no significant effect on inflammation in these areas. This is the first study proving a sex-dependent association between dopamine dysfunction and inflammation in specific brain areas, hence leading to different behavioral outcomes in a mouse model of ADHD. These findings provide new clues for potential treatments for ADHD.

Place, publisher, year, edition, pages
MDPI, 2023. Vol. 12, no 3, p. 465-486
Keywords [en]
attention deficit/hyperactivity disorder (ADHD); microglia; oxidative stress; Ape1; pain sensitivity; hyperactivity; novel object recognition; spatial memory; neuroinflammation
National Category
Nursing
Research subject
NURSING AND PUBLIC HEALTH SCIENCE, Nursing science
Identifiers
URN: urn:nbn:se:hv:diva-19635DOI: 10.3390/cells12030465ISI: 000929256800001PubMedID: 36766806Scopus ID: 2-s2.0-85147881244OAI: oai:DiVA.org:hv-19635DiVA, id: diva2:1736751
Note

This article belongs to the Special Issue The Signaling and Cellular Mechanisms of Pain.

 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)

Available from: 2023-02-14 Created: 2023-02-14 Last updated: 2024-01-12Bibliographically approved

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Kerekes, Nora

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