University of Worcester Worcester Research and Publications

Tetracosahexaenoylethanolamide, a novel -acylethanolamide, is elevated in ischemia and increases neuronal output.

Lin, L., Metherel, A.H., Di Miceli, Mathieu ORCID:, Liu, Z., Sahin, C., Fioramonti, X,, Cummins, C.L., Layé, S. and Bazinet, R.P. (2020) Tetracosahexaenoylethanolamide, a novel -acylethanolamide, is elevated in ischemia and increases neuronal output. Journal of lipid research, 61 (11). pp. 1480-1490. ISSN Print: 0022-2275 Online: 1539-7262

Lin Metherel Di Miceli Fioramonti Bazinet J Lipd Res 2021.pdf - Published Version
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-acylethanolamines (NAEs) are endogenous lipid-signaling molecules derived from fatty acids that regulate numerous biological functions, including in the brain. Interestingly, NAEs are elevated in the absence of fatty acid amide hydrolase (FAAH) and following CO-induced ischemia/hypercapnia, suggesting a neuroprotective response. Tetracosahexaenoic acid (THA) is a product and precursor to DHA; however, the NAE product, tetracosahexaenoylethanolamide (THEA), has never been reported. Presently, THEA was chemically synthesized as an authentic standard to confirm THEA presence in biological tissues. Whole brains were collected and analyzed for unesterified THA, total THA, and THEA in wild-type and FAAH-KO mice that were euthanized by either head-focused microwave fixation, CO + microwave, or CO only. PPAR activity by transient transfection assay and ex vivo neuronal output in medium spiny neurons (MSNs) of the nucleus accumbens by patch clamp electrophysiology were determined following THEA exposure. THEA in the wild-type mice was nearly doubled ( < 0.05) following ischemia/hypercapnia (CO euthanization) and up to 12 times higher ( < 0.001) in the FAAH-KO compared with wild-type. THEA did not increase ( > 0.05) transcriptional activity of PPARs relative to control, but 100 nM of THEA increased ( < 0.001) neuronal output in MSNs of the nucleus accumbens. Here were identify a novel NAE, THEA, in the brain that is elevated upon ischemia/hypercapnia and by KO of the FAAH enzyme. While THEA did not activate PPAR, it augmented the excitability of MSNs in the nucleus accumbens. Overall, our results suggest that THEA is a novel NAE that is produced in the brain upon ischemia/hypercapnia and regulates neuronal excitation.

Item Type: Article
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Uncontrolled Discrete Keywords: tetracosahexaenoic acid, fatty acid amide hydrolase, patch clamp, neurons, brain lipids, fatty acid, fatty acid metabolism, peroxisome proliferator-activated receptors, fatty acid amide hydrolase-knockout
Divisions: College of Health, Life and Environmental Sciences > School of Science and the Environment
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Copyright Info: Open Access article
Depositing User: Mathieu Di Miceli
Date Deposited: 06 Oct 2021 11:18
Last Modified: 07 Dec 2021 16:50

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