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Altered brain levels of arachidonic acid-derived inflammatory eicosanoids in a rodent model of anorexia nervosa.
- Source :
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Biochimica et biophysica acta. Molecular and cell biology of lipids [Biochim Biophys Acta Mol Cell Biol Lipids] 2020 Apr; Vol. 1865 (4), pp. 158578. Date of Electronic Publication: 2019 Nov 26. - Publication Year :
- 2020
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Abstract
- Increasing evidence underline the role of inflammation in the behavioral, emotional and cognitive dysregulations displayed in anorexia nervosa (AN). Among the inflammatory mediators acting at both peripheral and central levels, growing attention receives a class of lipids derived from arachidonic acid (AA), called eicosanoids (eiCs), which exert a complex, multifaceted role in a wide range of neuroinflammatory processes, peripheral inflammation, and generally in immune system function. To date, little is known about their possible involvement in the neurobiological underpinnings of AN. The present study evaluated whether the activity-based model of AN (ABA) may alter AA-metabolic pathways by changing the levels of AA-derived eiCs in specific brain areas implicated in the development of the typical anorexic-like phenotype, i.e. in prefrontal cortex, cerebral cortex, nucleus accumbens, caudate putamen, amygdala, hippocampus, hypothalamus and cerebellum. Our results point to brain region-specific alterations of the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 epoxygenase (CYP) metabolic pathways rendering altered levels of AA-derived eiCs (i.e. prostaglandins, thromboxanes and hydroxyeicosatetraenoic acids) in response to induction of and recovery from the ABA condition. These changes, supported by altered messenger RNA (mRNA) levels of genes coding for enzymes involved in eiCs-related methabolic pathways (i.e., PLA <subscript>2</subscript> , COX-2, 5-LOX and 15-LOX), underlie a widespread brain dysregulation of pro- and anti-inflammatory eiC-mediated processes in the ABA model of AN. These data suggest the importance of eiCs signaling within corticolimbic areas in regulating key neurobehavioral functions and highlight eiCs as biomarker candidates for monitoring the onset and development of AN, and/or as possible targets for pharmacological management.<br />Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare.<br /> (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Anorexia Nervosa metabolism
Arachidonic Acid metabolism
Brain metabolism
Disease Models, Animal
Eicosanoids metabolism
Female
Inflammation metabolism
Metabolic Networks and Pathways
Rats, Sprague-Dawley
Anorexia Nervosa pathology
Arachidonic Acid analysis
Brain pathology
Eicosanoids analysis
Inflammation pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-2618
- Volume :
- 1865
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta. Molecular and cell biology of lipids
- Publication Type :
- Academic Journal
- Accession number :
- 31778792
- Full Text :
- https://doi.org/10.1016/j.bbalip.2019.158578