在多发性硬化症动物模型中神经元特异性缺失 C16 神经酰胺合成酶的神经保护作用。

IF 5.4 2区 医学 Q1 NEUROSCIENCES
Glia Pub Date : 2025-02-01 Epub Date: 2024-11-03 DOI:10.1002/glia.24631
Mario Amatruda, Damien Marechal, Mar Gacias, Maureen Wentling, Sarah Turpin-Nolan, Johannes Morstein, Mohammed Moniruzzaman, Jens C Brüning, Norman J Haughey, Dirk H Trauner, Patrizia Casaccia
{"title":"在多发性硬化症动物模型中神经元特异性缺失 C16 神经酰胺合成酶的神经保护作用。","authors":"Mario Amatruda, Damien Marechal, Mar Gacias, Maureen Wentling, Sarah Turpin-Nolan, Johannes Morstein, Mohammed Moniruzzaman, Jens C Brüning, Norman J Haughey, Dirk H Trauner, Patrizia Casaccia","doi":"10.1002/glia.24631","DOIUrl":null,"url":null,"abstract":"<p><p>Ceramide C16 is a sphingolipid detected at high levels in several neurodegenerative disorders, including multiple sclerosis (MS). It can be generated de novo or from the hydrolysis of other sphingolipids, such as sphingomyelin or through the recycling of sphingosine, in what is known as the salvage pathway. While the myelin damage occurring in MS suggests the importance of the hydrolytic and salvage pathways, the growing interest on the importance of diet in demyelinating disorders, prompted us to investigate the involvement of de novo ceramide C16 synthesis on disease severity. A diet rich in saturated fats such as palmitic acid, as found in many highly processed foods, provides substrates for the ceramide C16 synthetic enzymes ceramide synthase 6 (CERS6) and 5 (CERS5), which are expressed in the central nervous system. Using the experimental autoimmune encephalomyelitis (EAE) model of inflammatory demyelination, we show here that mice with CamK2a+ neuronal specific deletion of both CerS6 and CerS5 show a milder course of EAE than wild type mice, even when fed a diet enriched in palmitic acid. At a cellular level, neurons lacking both CerS6 and CerS5 are protected from the mitochondrial dysfunction arising from exposure to oxidative stress and palmitic acid in the medium. These data underscore the importance of a healthy diet avoiding processed foods for demyelinating disorders and identifies endogenous neuronal synthesis of ceramide C16 as an important determinant of disease severity.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":"271-290"},"PeriodicalIF":5.4000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Neuroprotective effect of neuron-specific deletion of the C16 ceramide synthetic enzymes in an animal model of multiple sclerosis.\",\"authors\":\"Mario Amatruda, Damien Marechal, Mar Gacias, Maureen Wentling, Sarah Turpin-Nolan, Johannes Morstein, Mohammed Moniruzzaman, Jens C Brüning, Norman J Haughey, Dirk H Trauner, Patrizia Casaccia\",\"doi\":\"10.1002/glia.24631\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Ceramide C16 is a sphingolipid detected at high levels in several neurodegenerative disorders, including multiple sclerosis (MS). It can be generated de novo or from the hydrolysis of other sphingolipids, such as sphingomyelin or through the recycling of sphingosine, in what is known as the salvage pathway. While the myelin damage occurring in MS suggests the importance of the hydrolytic and salvage pathways, the growing interest on the importance of diet in demyelinating disorders, prompted us to investigate the involvement of de novo ceramide C16 synthesis on disease severity. A diet rich in saturated fats such as palmitic acid, as found in many highly processed foods, provides substrates for the ceramide C16 synthetic enzymes ceramide synthase 6 (CERS6) and 5 (CERS5), which are expressed in the central nervous system. Using the experimental autoimmune encephalomyelitis (EAE) model of inflammatory demyelination, we show here that mice with CamK2a+ neuronal specific deletion of both CerS6 and CerS5 show a milder course of EAE than wild type mice, even when fed a diet enriched in palmitic acid. At a cellular level, neurons lacking both CerS6 and CerS5 are protected from the mitochondrial dysfunction arising from exposure to oxidative stress and palmitic acid in the medium. These data underscore the importance of a healthy diet avoiding processed foods for demyelinating disorders and identifies endogenous neuronal synthesis of ceramide C16 as an important determinant of disease severity.</p>\",\"PeriodicalId\":174,\"journal\":{\"name\":\"Glia\",\"volume\":\" \",\"pages\":\"271-290\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2025-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Glia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/glia.24631\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Glia","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/glia.24631","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/3 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0

摘要

神经酰胺 C16 是一种鞘脂,在包括多发性硬化症(MS)在内的多种神经退行性疾病中含量较高。它可以从头生成,也可以通过水解其他鞘磷脂(如鞘磷脂)或回收鞘磷脂生成,这就是所谓的挽救途径。多发性硬化症的髓鞘损伤表明了水解和挽救途径的重要性,而饮食对脱髓鞘疾病的重要性也日益受到关注,这促使我们研究神经酰胺 C16 的从头合成对疾病严重程度的影响。许多高度加工食品中含有丰富的饱和脂肪(如棕榈酸),这为中枢神经系统中表达的神经酰胺 C16 合成酶神经酰胺合成酶 6(CERS6)和 5(CERS5)提供了底物。我们利用实验性自身免疫性脑脊髓炎(EAE)模型来研究炎性脱髓鞘,结果表明,CamK2a+神经元特异性缺失CerS6和CerS5的小鼠的EAE病程比野生型小鼠轻,即使喂食富含棕榈酸的食物也是如此。在细胞水平上,同时缺失 CerS6 和 CerS5 的神经元受到保护,不会因暴露于氧化应激和培养基中的棕榈酸而导致线粒体功能障碍。这些数据强调了避免食用加工食品的健康饮食对脱髓鞘疾病的重要性,并确定神经元内源性神经酰胺 C16 的合成是决定疾病严重程度的重要因素。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Neuroprotective effect of neuron-specific deletion of the C16 ceramide synthetic enzymes in an animal model of multiple sclerosis.

Ceramide C16 is a sphingolipid detected at high levels in several neurodegenerative disorders, including multiple sclerosis (MS). It can be generated de novo or from the hydrolysis of other sphingolipids, such as sphingomyelin or through the recycling of sphingosine, in what is known as the salvage pathway. While the myelin damage occurring in MS suggests the importance of the hydrolytic and salvage pathways, the growing interest on the importance of diet in demyelinating disorders, prompted us to investigate the involvement of de novo ceramide C16 synthesis on disease severity. A diet rich in saturated fats such as palmitic acid, as found in many highly processed foods, provides substrates for the ceramide C16 synthetic enzymes ceramide synthase 6 (CERS6) and 5 (CERS5), which are expressed in the central nervous system. Using the experimental autoimmune encephalomyelitis (EAE) model of inflammatory demyelination, we show here that mice with CamK2a+ neuronal specific deletion of both CerS6 and CerS5 show a milder course of EAE than wild type mice, even when fed a diet enriched in palmitic acid. At a cellular level, neurons lacking both CerS6 and CerS5 are protected from the mitochondrial dysfunction arising from exposure to oxidative stress and palmitic acid in the medium. These data underscore the importance of a healthy diet avoiding processed foods for demyelinating disorders and identifies endogenous neuronal synthesis of ceramide C16 as an important determinant of disease severity.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Glia
Glia 医学-神经科学
CiteScore
13.10
自引率
4.80%
发文量
162
审稿时长
3-8 weeks
期刊介绍: GLIA is a peer-reviewed journal, which publishes articles dealing with all aspects of glial structure and function. This includes all aspects of glial cell biology in health and disease.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信