Zsófia Sziber , Paula Torrents-Solé , Aleksandar Kovacevic , Josef P. Kapfhammer
{"title":"蛋白激酶C γ在脊髓小脑性共济失调小鼠模型中调节浦肯野细胞树突棘的发育","authors":"Zsófia Sziber , Paula Torrents-Solé , Aleksandar Kovacevic , Josef P. Kapfhammer","doi":"10.1016/j.expneurol.2025.115377","DOIUrl":null,"url":null,"abstract":"<div><div>The formation and proper organization of synaptic connections in the Purkinje cell dendritic tree are essential for cerebellar function and are often disrupted in cerebellar diseases, particularly in spinocerebellar ataxia (SCA). In this study, we utilized two distinct mouse models of SCA14, a subtype of SCA caused by point mutations in the protein kinase C gamma (PKCγ) gene, which plays an important role in regulating the dendritic architecture in Purkinje cells. We investigated the development of Purkinje cell dendritic spines in organotypic slice cultures from control, PKCγ knockout (PKCγ-KO) mice, and the two SCA14 models to further elucidate the role of PKCγ activity in dendritic spine formation. Our results revealed that the loss of PKCγ had only minor effects on dendritic spines, likely due to compensatory mechanisms mediated by PKCα. In contrast, elevated PKCγ activity—either induced pharmacologically in control mice or resulting from the expression of mutated PKCγ in the SCA14 models—led to a significant loss of dendritic spines. Furthermore, increased PKCγ activity impaired spine enlargement and maturation by reducing the number of mature, mushroom-shaped spines. These findings demonstrate that PKCγ regulates dendritic spine formation, a crucial process for synapse establishment and the proper function of cerebellar Purkinje cells.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"393 ","pages":"Article 115377"},"PeriodicalIF":4.2000,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Protein kinase C gamma regulates Purkinje cell dendritic spine development in a mouse model of spinocerebellar ataxia\",\"authors\":\"Zsófia Sziber , Paula Torrents-Solé , Aleksandar Kovacevic , Josef P. Kapfhammer\",\"doi\":\"10.1016/j.expneurol.2025.115377\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The formation and proper organization of synaptic connections in the Purkinje cell dendritic tree are essential for cerebellar function and are often disrupted in cerebellar diseases, particularly in spinocerebellar ataxia (SCA). In this study, we utilized two distinct mouse models of SCA14, a subtype of SCA caused by point mutations in the protein kinase C gamma (PKCγ) gene, which plays an important role in regulating the dendritic architecture in Purkinje cells. We investigated the development of Purkinje cell dendritic spines in organotypic slice cultures from control, PKCγ knockout (PKCγ-KO) mice, and the two SCA14 models to further elucidate the role of PKCγ activity in dendritic spine formation. Our results revealed that the loss of PKCγ had only minor effects on dendritic spines, likely due to compensatory mechanisms mediated by PKCα. In contrast, elevated PKCγ activity—either induced pharmacologically in control mice or resulting from the expression of mutated PKCγ in the SCA14 models—led to a significant loss of dendritic spines. Furthermore, increased PKCγ activity impaired spine enlargement and maturation by reducing the number of mature, mushroom-shaped spines. These findings demonstrate that PKCγ regulates dendritic spine formation, a crucial process for synapse establishment and the proper function of cerebellar Purkinje cells.</div></div>\",\"PeriodicalId\":12246,\"journal\":{\"name\":\"Experimental Neurology\",\"volume\":\"393 \",\"pages\":\"Article 115377\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2025-07-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Experimental Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0014488625002419\",\"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":"Experimental Neurology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014488625002419","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Protein kinase C gamma regulates Purkinje cell dendritic spine development in a mouse model of spinocerebellar ataxia
The formation and proper organization of synaptic connections in the Purkinje cell dendritic tree are essential for cerebellar function and are often disrupted in cerebellar diseases, particularly in spinocerebellar ataxia (SCA). In this study, we utilized two distinct mouse models of SCA14, a subtype of SCA caused by point mutations in the protein kinase C gamma (PKCγ) gene, which plays an important role in regulating the dendritic architecture in Purkinje cells. We investigated the development of Purkinje cell dendritic spines in organotypic slice cultures from control, PKCγ knockout (PKCγ-KO) mice, and the two SCA14 models to further elucidate the role of PKCγ activity in dendritic spine formation. Our results revealed that the loss of PKCγ had only minor effects on dendritic spines, likely due to compensatory mechanisms mediated by PKCα. In contrast, elevated PKCγ activity—either induced pharmacologically in control mice or resulting from the expression of mutated PKCγ in the SCA14 models—led to a significant loss of dendritic spines. Furthermore, increased PKCγ activity impaired spine enlargement and maturation by reducing the number of mature, mushroom-shaped spines. These findings demonstrate that PKCγ regulates dendritic spine formation, a crucial process for synapse establishment and the proper function of cerebellar Purkinje cells.
期刊介绍:
Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.