Targeting Neuroinflammation with Abscisic Acid Reduces Pain Sensitivity in Females and Hyperactivity in Males of an ADHD Mice Model

被引:8
作者
Meseguer-Beltran, Maria [1 ,2 ]
Sanchez-Sarasua, Sandra [2 ,3 ]
Landry, Marc [3 ]
Kerekes, Nora [4 ]
Sanchez-Perez, Ana Maria [1 ,2 ]
机构
[1] Univ Jaume 1, Insitute Adv Mat INAM, Castellon de La Plana 12071, Spain
[2] Univ Jaume 1, Fac Hlth Sci, Castellon de La Plana 12071, Spain
[3] Univ Bordeaux, Inst Neurodegenerat Dis, CNRS, UMR 5293, F-33000 Bordeaux, France
[4] Univ West, Dept Hlth Sci, S-46186 Trollhattan, Sweden
关键词
attention deficit; hyperactivity disorder (ADHD); microglia; oxidative stress; Ape1; pain sensitivity; hyperactivity; novel object recognition; spatial memory; neuroinflammation; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; APURINIC/APYRIMIDINIC ENDONUCLEASE-1; SEX-DIFFERENCES; MOUSE MODEL; INFLAMMATION; DYSFUNCTION; INHIBITION; IMPAIRMENT; PERCEPTION; SYMPTOMS;
D O I
10.3390/cells12030465
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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页数:20
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共 98 条
[1]  
Agarwal Rashi, 2012, Innov Clin Neurosci, V9, P10
[2]   Attention-Deficit/Hyperactivity Disorder And Inflammation: What Does Current Knowledge Tell Us? A Systematic Review [J].
Anand, Deepa ;
Colpo, Gabriela D. ;
Zeni, Gregory ;
Zeni, Cristian P. ;
Teixeira, Antonio L. .
FRONTIERS IN PSYCHIATRY, 2017, 8
[3]   Self-Regulation of Emotion, Functional Impairment, and Comorbidity Among ChildrenWith AD/HD [J].
Anastopoulos, Arthur D. ;
Smith, Taylor F. ;
Garrett, Melanie E. ;
Morrissey-Kane, Erin ;
Schatz, Nicole K. ;
Sommer, Jennifer L. ;
Kollins, Scott H. ;
Ashley-Koch, Allison .
JOURNAL OF ATTENTION DISORDERS, 2011, 15 (07) :583-592
[4]   Chronic Pain And Health-Related Quality Of Life In Women With Autism And/Or ADHD: A Prospective Longitudinal Study [J].
Asztely, Karin ;
Kopp, Svenny ;
Gillberg, Christopher ;
Waern, Margda ;
Bergman, Stefan .
JOURNAL OF PAIN RESEARCH, 2019, 12 :2925-2932
[5]   The dopamine D4 receptor is essential for hyperactivity and impaired behavioral inhibition in a mouse model of attention deficit/hyperactivity disorder [J].
Avale, ME ;
Falzone, TL ;
Gelman, DM ;
Low, MJ ;
Grandy, DK ;
Rubinstein, M .
MOLECULAR PSYCHIATRY, 2004, 9 (07) :718-726
[6]   The Presence of Comorbid ADHD and Anxiety Symptoms in Autism Spectrum Disorder: Clinical Presentation and Predictors [J].
Avni, Einat ;
Ben-Itzchak, Esther ;
Zachoro, Ditza A. .
FRONTIERS IN PSYCHIATRY, 2018, 9
[7]   Anterior insular cortex mediates hyperalgesia induced by chronic pancreatitis in rats [J].
Bai, Yang ;
Ma, Li-Tian ;
Chen, Yan-Bing ;
Ren, Dan ;
Chen, Ying-Biao ;
Li, Ying-Qi ;
Sun, Hong-Ke ;
Qiu, Xin-Tong ;
Zhang, Ting ;
Zhang, Ming-Ming ;
Yi, Xi-Nan ;
Chen, Tao ;
Li, Hui ;
Fan, Bo-Yuan ;
Li, Yun-Qing .
MOLECULAR BRAIN, 2019, 12 (01)
[8]   Inflammation in psychiatric disorders: what comes first? [J].
Bauer, Moises E. ;
Teixeira, Antonio L. .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 2019, 1437 (01) :57-67
[9]   Cerebral interactions of pain and reward and their relevance for chronic pain [J].
Becker, Susanne ;
Gandhi, Wiebke ;
Schweinhardt, Petra .
NEUROSCIENCE LETTERS, 2012, 520 (02) :182-187
[10]   Cognitive, emotional, and social functioning of preschoolers with attention deficit hyperactivity problems [J].
Biele, Guido ;
Overgaard, Kristin R. ;
Friis, Svein ;
Zeiner, Pal ;
Aase, Heidi .
BMC PSYCHIATRY, 2022, 22 (01)