Luca Lo Piccolo , Ranchana Yeewa , Sureena Pohsa , Titaree Yamsri , Daniel Calovi , Jutarop Phetcharaburanin , Manida Suksawat , Thanaporn Kulthawatsiri , Vorasuk Shotelersuk , Salinee Jantrapirom
{"title":"敲除 FAME4-associating YEATS2 会损害黑腹果蝇多巴胺能突触的完整性并导致癫痫样行为","authors":"Luca Lo Piccolo , Ranchana Yeewa , Sureena Pohsa , Titaree Yamsri , Daniel Calovi , Jutarop Phetcharaburanin , Manida Suksawat , Thanaporn Kulthawatsiri , Vorasuk Shotelersuk , Salinee Jantrapirom","doi":"10.1016/j.pneurobio.2023.102558","DOIUrl":null,"url":null,"abstract":"<div><p><span>Familial adult myoclonus epilepsy (FAME) is a neurological disorder caused by a </span><em>TTTTA/TTTCA</em> intronic repeat expansion. FAME4 is one of the six types of FAME that results from the repeat expansion in the first intron of the gene <em>YEATS2</em>. Although the RNA toxicity is believed to be the primary mechanism underlying FAME, the role of genes where repeat expansions reside is still unclear, particularly in the case of YEATS2 in neurons. This study used <em>Drosophila</em> to explore the effects of reducing <em>YEATS2</em> expression. Two pan-neuronally driven <em>dsDNA</em> were used for knockdown of <em>Drosophila YEATS2</em> (<em>dYEATS2</em>), and the resulting molecular and behavioural outcomes were evaluated. <em>Drosophila</em> with reduced <em>dYEATS2</em> expression exhibited decreased tolerance to acute stress, disturbed locomotion, abnormal social behaviour, and decreased motivated activity. Additionally, reducing <em>dYEATS2</em> expression negatively affected <span><em>tyrosine hydroxylase</em></span> (<em>TH</em><span>) gene expression, resulting in decreased dopamine biosynthesis. Remarkably, seizure-like behaviours induced by knocking down </span><em>dYEATS2</em><span> were rescued by the administration of L-DOPA. This study reveals a novel role of YEATS2 in neurons in regulating acute stress responses, locomotion, and complex behaviours, and suggests that haploinsufficiency of YEATS2 may play a role in FAME4.</span></p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"233 ","pages":"Article 102558"},"PeriodicalIF":6.7000,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"FAME4-associating YEATS2 knockdown impairs dopaminergic synaptic integrity and leads to seizure-like behaviours in Drosophila melanogaster\",\"authors\":\"Luca Lo Piccolo , Ranchana Yeewa , Sureena Pohsa , Titaree Yamsri , Daniel Calovi , Jutarop Phetcharaburanin , Manida Suksawat , Thanaporn Kulthawatsiri , Vorasuk Shotelersuk , Salinee Jantrapirom\",\"doi\":\"10.1016/j.pneurobio.2023.102558\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span>Familial adult myoclonus epilepsy (FAME) is a neurological disorder caused by a </span><em>TTTTA/TTTCA</em> intronic repeat expansion. FAME4 is one of the six types of FAME that results from the repeat expansion in the first intron of the gene <em>YEATS2</em>. Although the RNA toxicity is believed to be the primary mechanism underlying FAME, the role of genes where repeat expansions reside is still unclear, particularly in the case of YEATS2 in neurons. This study used <em>Drosophila</em> to explore the effects of reducing <em>YEATS2</em> expression. Two pan-neuronally driven <em>dsDNA</em> were used for knockdown of <em>Drosophila YEATS2</em> (<em>dYEATS2</em>), and the resulting molecular and behavioural outcomes were evaluated. <em>Drosophila</em> with reduced <em>dYEATS2</em> expression exhibited decreased tolerance to acute stress, disturbed locomotion, abnormal social behaviour, and decreased motivated activity. Additionally, reducing <em>dYEATS2</em> expression negatively affected <span><em>tyrosine hydroxylase</em></span> (<em>TH</em><span>) gene expression, resulting in decreased dopamine biosynthesis. Remarkably, seizure-like behaviours induced by knocking down </span><em>dYEATS2</em><span> were rescued by the administration of L-DOPA. This study reveals a novel role of YEATS2 in neurons in regulating acute stress responses, locomotion, and complex behaviours, and suggests that haploinsufficiency of YEATS2 may play a role in FAME4.</span></p></div>\",\"PeriodicalId\":20851,\"journal\":{\"name\":\"Progress in Neurobiology\",\"volume\":\"233 \",\"pages\":\"Article 102558\"},\"PeriodicalIF\":6.7000,\"publicationDate\":\"2023-12-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Progress in Neurobiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0301008223001594\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Progress in Neurobiology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0301008223001594","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
FAME4-associating YEATS2 knockdown impairs dopaminergic synaptic integrity and leads to seizure-like behaviours in Drosophila melanogaster
Familial adult myoclonus epilepsy (FAME) is a neurological disorder caused by a TTTTA/TTTCA intronic repeat expansion. FAME4 is one of the six types of FAME that results from the repeat expansion in the first intron of the gene YEATS2. Although the RNA toxicity is believed to be the primary mechanism underlying FAME, the role of genes where repeat expansions reside is still unclear, particularly in the case of YEATS2 in neurons. This study used Drosophila to explore the effects of reducing YEATS2 expression. Two pan-neuronally driven dsDNA were used for knockdown of Drosophila YEATS2 (dYEATS2), and the resulting molecular and behavioural outcomes were evaluated. Drosophila with reduced dYEATS2 expression exhibited decreased tolerance to acute stress, disturbed locomotion, abnormal social behaviour, and decreased motivated activity. Additionally, reducing dYEATS2 expression negatively affected tyrosine hydroxylase (TH) gene expression, resulting in decreased dopamine biosynthesis. Remarkably, seizure-like behaviours induced by knocking down dYEATS2 were rescued by the administration of L-DOPA. This study reveals a novel role of YEATS2 in neurons in regulating acute stress responses, locomotion, and complex behaviours, and suggests that haploinsufficiency of YEATS2 may play a role in FAME4.
期刊介绍:
Progress in Neurobiology is an international journal that publishes groundbreaking original research, comprehensive review articles and opinion pieces written by leading researchers. The journal welcomes contributions from the broad field of neuroscience that apply neurophysiological, biochemical, pharmacological, molecular biological, anatomical, computational and behavioral analyses to problems of molecular, cellular, developmental, systems, and clinical neuroscience.