Sophie Simard, Reza Rahimian, Maria Antonietta Davoli, Stéphanie Théberge, Natalie Matosin, Gustavo Turecki, Corina Nagy, Naguib Mechawar
{"title":"人脑成年海马神经发生的空间转录组分析","authors":"Sophie Simard, Reza Rahimian, Maria Antonietta Davoli, Stéphanie Théberge, Natalie Matosin, Gustavo Turecki, Corina Nagy, Naguib Mechawar","doi":"10.1503/jpn.240026","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Adult hippocampal neurogenesis has been extensively characterized in rodent models, but its existence in humans remains controversial. We sought to assess the phenomenon in postmortem human hippocampal samples by combining spatial transcriptomics and multiplexed fluorescent in situ hybridization.</p><p><strong>Methods: </strong>We computationally examined the spatial expression of various canonical neurogenesis markers in postmortem dentate gyrus (DG) sections from young and middle-aged sudden-death males. We conducted in situ assessment of markers expressed in neural stem cells, proliferative cells, and immature granule neurons in postmortem DG sections from infant, adolescent, and middle-aged males.</p><p><strong>Results: </strong>We examined frozen DG tissue from infant (<i>n</i> = 1, age 2 yr), adolescent (<i>n</i> = 1, age 16 yr), young adult (<i>n</i> = 2, mean age 23.5 yr), and middle-aged (<i>n</i> = 2, mean age 42.5 yr) males, and frozen-fixed DG tissue from middle-aged males (<i>n</i> = 6, mean age 43.5 yr). We detected very few cells expressing neural stem cell and proliferative markers in the human DG from childhood to middle age. However, at all ages, we observed a substantial number of DG cells expressing the immature neuronal marker <i>DCX</i>. Most <i>DCX</i> <sup>+</sup> cells displayed an inhibitory phenotype, while the remainder were non-committed or excitatory in nature.</p><p><strong>Limitations: </strong>The study was limited by small sample sizes and included samples only from males.</p><p><strong>Conclusion: </strong>Our findings indicate very low levels of hippocampal neurogenesis throughout life and the existence of a local reserve of plasticity in the adult human hippocampus. Overall, our study provides important insight into the distribution and phenotype of cells expressing neurogenesis markers in the adult human hippocampus.</p>","PeriodicalId":50073,"journal":{"name":"Journal of Psychiatry & Neuroscience","volume":"49 5","pages":"E319-E333"},"PeriodicalIF":4.1000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495544/pdf/","citationCount":"0","resultStr":"{\"title\":\"Spatial transcriptomic analysis of adult hippocampal neurogenesis in the human brain.\",\"authors\":\"Sophie Simard, Reza Rahimian, Maria Antonietta Davoli, Stéphanie Théberge, Natalie Matosin, Gustavo Turecki, Corina Nagy, Naguib Mechawar\",\"doi\":\"10.1503/jpn.240026\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Adult hippocampal neurogenesis has been extensively characterized in rodent models, but its existence in humans remains controversial. We sought to assess the phenomenon in postmortem human hippocampal samples by combining spatial transcriptomics and multiplexed fluorescent in situ hybridization.</p><p><strong>Methods: </strong>We computationally examined the spatial expression of various canonical neurogenesis markers in postmortem dentate gyrus (DG) sections from young and middle-aged sudden-death males. We conducted in situ assessment of markers expressed in neural stem cells, proliferative cells, and immature granule neurons in postmortem DG sections from infant, adolescent, and middle-aged males.</p><p><strong>Results: </strong>We examined frozen DG tissue from infant (<i>n</i> = 1, age 2 yr), adolescent (<i>n</i> = 1, age 16 yr), young adult (<i>n</i> = 2, mean age 23.5 yr), and middle-aged (<i>n</i> = 2, mean age 42.5 yr) males, and frozen-fixed DG tissue from middle-aged males (<i>n</i> = 6, mean age 43.5 yr). We detected very few cells expressing neural stem cell and proliferative markers in the human DG from childhood to middle age. However, at all ages, we observed a substantial number of DG cells expressing the immature neuronal marker <i>DCX</i>. Most <i>DCX</i> <sup>+</sup> cells displayed an inhibitory phenotype, while the remainder were non-committed or excitatory in nature.</p><p><strong>Limitations: </strong>The study was limited by small sample sizes and included samples only from males.</p><p><strong>Conclusion: </strong>Our findings indicate very low levels of hippocampal neurogenesis throughout life and the existence of a local reserve of plasticity in the adult human hippocampus. Overall, our study provides important insight into the distribution and phenotype of cells expressing neurogenesis markers in the adult human hippocampus.</p>\",\"PeriodicalId\":50073,\"journal\":{\"name\":\"Journal of Psychiatry & Neuroscience\",\"volume\":\"49 5\",\"pages\":\"E319-E333\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2024-10-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495544/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Psychiatry & Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1503/jpn.240026\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/1 0:00:00\",\"PubModel\":\"Print\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Psychiatry & Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1503/jpn.240026","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/1 0:00:00","PubModel":"Print","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Spatial transcriptomic analysis of adult hippocampal neurogenesis in the human brain.
Background: Adult hippocampal neurogenesis has been extensively characterized in rodent models, but its existence in humans remains controversial. We sought to assess the phenomenon in postmortem human hippocampal samples by combining spatial transcriptomics and multiplexed fluorescent in situ hybridization.
Methods: We computationally examined the spatial expression of various canonical neurogenesis markers in postmortem dentate gyrus (DG) sections from young and middle-aged sudden-death males. We conducted in situ assessment of markers expressed in neural stem cells, proliferative cells, and immature granule neurons in postmortem DG sections from infant, adolescent, and middle-aged males.
Results: We examined frozen DG tissue from infant (n = 1, age 2 yr), adolescent (n = 1, age 16 yr), young adult (n = 2, mean age 23.5 yr), and middle-aged (n = 2, mean age 42.5 yr) males, and frozen-fixed DG tissue from middle-aged males (n = 6, mean age 43.5 yr). We detected very few cells expressing neural stem cell and proliferative markers in the human DG from childhood to middle age. However, at all ages, we observed a substantial number of DG cells expressing the immature neuronal marker DCX. Most DCX+ cells displayed an inhibitory phenotype, while the remainder were non-committed or excitatory in nature.
Limitations: The study was limited by small sample sizes and included samples only from males.
Conclusion: Our findings indicate very low levels of hippocampal neurogenesis throughout life and the existence of a local reserve of plasticity in the adult human hippocampus. Overall, our study provides important insight into the distribution and phenotype of cells expressing neurogenesis markers in the adult human hippocampus.
期刊介绍:
The Journal of Psychiatry & Neuroscience publishes papers at the intersection of psychiatry and neuroscience that advance our understanding of the neural mechanisms involved in the etiology and treatment of psychiatric disorders. This includes studies on patients with psychiatric disorders, healthy humans, and experimental animals as well as studies in vitro. Original research articles, including clinical trials with a mechanistic component, and review papers will be considered.