{"title":"Hepatic Acyl CoA Oxidase1 Inhibition Modifies Brain Lipids and Electrical Properties of Dentate Gyrus.","authors":"Shahrbanoo Rafiei, Fariba Khodagholi, Hamid Gholami Pourbadie, Leila Dargahi, Fereshteh Motamedi","doi":"10.32598/bcn.2021.3500.1","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Peroxisomes are essential organelles in lipid metabolism. They contain enzymes for β-oxidation of very long-chain fatty acids (VLCFA) that cannot be broken down in mitochondria. Reduced expression in hepatic acyl-CoA oxidase 1 (ACOX1), a peroxisome β-oxidation enzyme, followed by modification of the brain fatty acid profile has been observed in aged rodents. These studies have suggested a potential role for peroxisome β-oxidation in brain aging. This study was designed to examine the effect of hepatic ACOX1 inhibition on brain fatty acid composition and neuronal cell activities of young rats (200-250 g).</p><p><strong>Methods: </strong>A specific ACOX1 inhibitor, 10, 12- tricosadiynoic acid (TDYA), 100 μg/kg (in olive oil) was administered by daily gavage for 25 days in male Wistar rats. The brain fatty acid composition and electrophysiological properties of dentate gyrus granule cells were determined using gas chromatography and whole-cell patch-clamp, respectively.</p><p><strong>Results: </strong>A significant increase in C20, C22, C18:1, C20:1, and a decrease of C18, C24, C20:3n6, and C22:6n3 were found in 10, 12- tricosadiynoic acid (TDYA) treated rats compared to the control group. The results showed that ACOX1 inhibition changes fatty acid composition similar to old rats. ACOX1 inhibition caused hyperpolarization of resting membrane potential, and also reduction of input resistance, action potential duration, and spike firing. Moreover, ACOX1 inhibition increased rheobase current and afterhyperpolarization amplitude in granule cells.</p><p><strong>Conclusion: </strong>The results indicated that systemic inhibition of ACOX1 causes hypo-excitability of neuronal cells. These results provide new evidence on the involvement of peroxisome function and hepatic ACOX1 activity in brain fatty acid profile and the electrophysiological properties of dentate gyrus cells.</p>","PeriodicalId":9483,"journal":{"name":"Canadian Journal of Forest Research","volume":"30 1","pages":"663-674"},"PeriodicalIF":1.7000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016873/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Canadian Journal of Forest Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.32598/bcn.2021.3500.1","RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"FORESTRY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Peroxisomes are essential organelles in lipid metabolism. They contain enzymes for β-oxidation of very long-chain fatty acids (VLCFA) that cannot be broken down in mitochondria. Reduced expression in hepatic acyl-CoA oxidase 1 (ACOX1), a peroxisome β-oxidation enzyme, followed by modification of the brain fatty acid profile has been observed in aged rodents. These studies have suggested a potential role for peroxisome β-oxidation in brain aging. This study was designed to examine the effect of hepatic ACOX1 inhibition on brain fatty acid composition and neuronal cell activities of young rats (200-250 g).
Methods: A specific ACOX1 inhibitor, 10, 12- tricosadiynoic acid (TDYA), 100 μg/kg (in olive oil) was administered by daily gavage for 25 days in male Wistar rats. The brain fatty acid composition and electrophysiological properties of dentate gyrus granule cells were determined using gas chromatography and whole-cell patch-clamp, respectively.
Results: A significant increase in C20, C22, C18:1, C20:1, and a decrease of C18, C24, C20:3n6, and C22:6n3 were found in 10, 12- tricosadiynoic acid (TDYA) treated rats compared to the control group. The results showed that ACOX1 inhibition changes fatty acid composition similar to old rats. ACOX1 inhibition caused hyperpolarization of resting membrane potential, and also reduction of input resistance, action potential duration, and spike firing. Moreover, ACOX1 inhibition increased rheobase current and afterhyperpolarization amplitude in granule cells.
Conclusion: The results indicated that systemic inhibition of ACOX1 causes hypo-excitability of neuronal cells. These results provide new evidence on the involvement of peroxisome function and hepatic ACOX1 activity in brain fatty acid profile and the electrophysiological properties of dentate gyrus cells.
期刊介绍：
Published since 1971, the Canadian Journal of Forest Research is a monthly journal that features articles, reviews, notes and concept papers on a broad spectrum of forest sciences, including biometrics, conservation, disturbances, ecology, economics, entomology, genetics, hydrology, management, nutrient cycling, pathology, physiology, remote sensing, silviculture, social sciences, soils, stand dynamics, and wood science, all in relation to the understanding or management of ecosystem services. It also publishes special issues dedicated to a topic of current interest.
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