Aishwarya Patwardhan, Siyao Li, Jessica Chen, Katrina Y Choe
{"title":"下丘脑室旁核催产素神经元的三维量化揭示了两种自闭症遗传小鼠模型的性别和亚区域特异性差异。","authors":"Aishwarya Patwardhan, Siyao Li, Jessica Chen, Katrina Y Choe","doi":"10.1111/jne.70092","DOIUrl":null,"url":null,"abstract":"<p><p>Oxytocin (OXT), a neuropeptide hormone essential to a wide range of social functions, has drawn increasing attention as a crucial contributor to the neurobiology of autism spectrum disorder (ASD). Central OXT system disruptions have been reported in several genetic mouse models of ASD; however, a detailed and systematic characterization of these phenotypes, and cross-model identification of shared and distinct features, are presently lacking. We integrated whole-brain OXT immunolabeling, SHIELD tissue clearing, light-sheet microscopy, and three-dimensional (3D) machine learning-based cell detection to establish a high-throughput, intact-tissue pipeline and quantified OXT immunopositive (OXT+) neurons across subregions of the paraventricular nucleus of the hypothalamus (PVN) in two genetic mouse models of ASD: Cntnap2 and Fmr1 knockout (KO) mice. We validated this pipeline alongside conventional immunohistochemistry using tissue sections. We show subregion- and sex-specific differences in PVN OXT+ cell counts in the two KO models. Notably, whole-PVN analysis revealed additional subregion- and sex-specific differences that were not evident in section-based quantification. These results identify subregion- and sex-specific differences in PVN OXT+ neuronal distribution as a shared phenotype in two genetic mouse models of ASD. This work highlights the importance of region-specific, high-resolution 3D approaches in intact tissue for quantifying cell populations within anatomically complex brain regions.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70092"},"PeriodicalIF":4.1000,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Three-dimensional quantification of oxytocin neurons in the hypothalamic paraventricular nucleus reveals sex- and subregion-specific differences in two genetic mouse models of autism.\",\"authors\":\"Aishwarya Patwardhan, Siyao Li, Jessica Chen, Katrina Y Choe\",\"doi\":\"10.1111/jne.70092\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Oxytocin (OXT), a neuropeptide hormone essential to a wide range of social functions, has drawn increasing attention as a crucial contributor to the neurobiology of autism spectrum disorder (ASD). Central OXT system disruptions have been reported in several genetic mouse models of ASD; however, a detailed and systematic characterization of these phenotypes, and cross-model identification of shared and distinct features, are presently lacking. We integrated whole-brain OXT immunolabeling, SHIELD tissue clearing, light-sheet microscopy, and three-dimensional (3D) machine learning-based cell detection to establish a high-throughput, intact-tissue pipeline and quantified OXT immunopositive (OXT+) neurons across subregions of the paraventricular nucleus of the hypothalamus (PVN) in two genetic mouse models of ASD: Cntnap2 and Fmr1 knockout (KO) mice. We validated this pipeline alongside conventional immunohistochemistry using tissue sections. We show subregion- and sex-specific differences in PVN OXT+ cell counts in the two KO models. Notably, whole-PVN analysis revealed additional subregion- and sex-specific differences that were not evident in section-based quantification. These results identify subregion- and sex-specific differences in PVN OXT+ neuronal distribution as a shared phenotype in two genetic mouse models of ASD. This work highlights the importance of region-specific, high-resolution 3D approaches in intact tissue for quantifying cell populations within anatomically complex brain regions.</p>\",\"PeriodicalId\":16535,\"journal\":{\"name\":\"Journal of Neuroendocrinology\",\"volume\":\" \",\"pages\":\"e70092\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2025-09-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neuroendocrinology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/jne.70092\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neuroendocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/jne.70092","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Three-dimensional quantification of oxytocin neurons in the hypothalamic paraventricular nucleus reveals sex- and subregion-specific differences in two genetic mouse models of autism.
Oxytocin (OXT), a neuropeptide hormone essential to a wide range of social functions, has drawn increasing attention as a crucial contributor to the neurobiology of autism spectrum disorder (ASD). Central OXT system disruptions have been reported in several genetic mouse models of ASD; however, a detailed and systematic characterization of these phenotypes, and cross-model identification of shared and distinct features, are presently lacking. We integrated whole-brain OXT immunolabeling, SHIELD tissue clearing, light-sheet microscopy, and three-dimensional (3D) machine learning-based cell detection to establish a high-throughput, intact-tissue pipeline and quantified OXT immunopositive (OXT+) neurons across subregions of the paraventricular nucleus of the hypothalamus (PVN) in two genetic mouse models of ASD: Cntnap2 and Fmr1 knockout (KO) mice. We validated this pipeline alongside conventional immunohistochemistry using tissue sections. We show subregion- and sex-specific differences in PVN OXT+ cell counts in the two KO models. Notably, whole-PVN analysis revealed additional subregion- and sex-specific differences that were not evident in section-based quantification. These results identify subregion- and sex-specific differences in PVN OXT+ neuronal distribution as a shared phenotype in two genetic mouse models of ASD. This work highlights the importance of region-specific, high-resolution 3D approaches in intact tissue for quantifying cell populations within anatomically complex brain regions.
期刊介绍:
Journal of Neuroendocrinology provides the principal international focus for the newest ideas in classical neuroendocrinology and its expanding interface with the regulation of behavioural, cognitive, developmental, degenerative and metabolic processes. Through the rapid publication of original manuscripts and provocative review articles, it provides essential reading for basic scientists and clinicians researching in this rapidly expanding field.
In determining content, the primary considerations are excellence, relevance and novelty. While Journal of Neuroendocrinology reflects the broad scientific and clinical interests of the BSN membership, the editorial team, led by Professor Julian Mercer, ensures that the journal’s ethos, authorship, content and purpose are those expected of a leading international publication.