Markus Höltje, Anton Wolkowicz, Irene Brunk, Jens Baron, Gudrun Ahnert-Hilger
{"title":"Gαo1和Gαo1/Gαo2缺失会对海马苔藓纤维束解剖结构和神经元形态发生产生不同影响。","authors":"Markus Höltje, Anton Wolkowicz, Irene Brunk, Jens Baron, Gudrun Ahnert-Hilger","doi":"10.1111/jnc.16248","DOIUrl":null,"url":null,"abstract":"<p><p>The heterotrimeric G-protein αo subunit is ubiquitously expressed in the CNS as two splice variants Gα<sub>o1</sub> and Gα<sub>o2</sub>, regulating various brain functions. Here, we investigated the effect of single Gα<sub>o1</sub>, Gα<sub>o2</sub>, and double Gα<sub>o1/2</sub> knockout on the postnatal development of the murine mossy fiber tract, a central pathway of the hippocampal connectivity circuit. The size of the hippocampal synaptic termination fields covered by mossy fiber boutons together with various fiber length parameters of the tract was analyzed by immunohistochemical staining of the vesicular Zinc transporter 3 (ZnT3) or Synaptoporin at postnatal days 2, 4, 8, 12, 16, and in the adult. Ultimately, Gα<sub>o1</sub> knockout resulted in a reduced developmental growth of synaptic mossy fiber terminal fields by 37% in the adult Stratum lucidum and by 30% in the total mossy fiber tract size. Other morphological parameters such as projection length of the infrapyramidal bundle of the tract were increased (+52% in Gα<sub>o1</sub> <sup>-/-</sup> mice). In contrast, Gα<sub>o2</sub> knockout had no effects on the mossy fiber tract. Moreover, by using primary heterozygous and homozygous Gα<sub>o1</sub> knockout hippocampal cultures, we detected a strongly pronounced reduction in axon and dendrite length (-50% and -38%, respectively) as well as axon and dendrite arborization complexity (-75% and -72% branch nodes, respectively) in the homozygous knockout. Deletion of both splice variants Gα<sub>o1</sub> and Gα<sub>o2</sub> partially rescued the in vivo and completely reconstituted the in vitro effects, indicating an opposing functional relevance of the two Gα<sub>o</sub> splice variants for neuronal development and synaptic connectivity.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":" ","pages":""},"PeriodicalIF":4.2000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Gα<sub>o1</sub> and Gα<sub>o1</sub>/Gα<sub>o2</sub> deletion differentially affect hippocampal mossy fiber tract anatomy and neuronal morphogenesis.\",\"authors\":\"Markus Höltje, Anton Wolkowicz, Irene Brunk, Jens Baron, Gudrun Ahnert-Hilger\",\"doi\":\"10.1111/jnc.16248\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The heterotrimeric G-protein αo subunit is ubiquitously expressed in the CNS as two splice variants Gα<sub>o1</sub> and Gα<sub>o2</sub>, regulating various brain functions. Here, we investigated the effect of single Gα<sub>o1</sub>, Gα<sub>o2</sub>, and double Gα<sub>o1/2</sub> knockout on the postnatal development of the murine mossy fiber tract, a central pathway of the hippocampal connectivity circuit. The size of the hippocampal synaptic termination fields covered by mossy fiber boutons together with various fiber length parameters of the tract was analyzed by immunohistochemical staining of the vesicular Zinc transporter 3 (ZnT3) or Synaptoporin at postnatal days 2, 4, 8, 12, 16, and in the adult. Ultimately, Gα<sub>o1</sub> knockout resulted in a reduced developmental growth of synaptic mossy fiber terminal fields by 37% in the adult Stratum lucidum and by 30% in the total mossy fiber tract size. Other morphological parameters such as projection length of the infrapyramidal bundle of the tract were increased (+52% in Gα<sub>o1</sub> <sup>-/-</sup> mice). In contrast, Gα<sub>o2</sub> knockout had no effects on the mossy fiber tract. Moreover, by using primary heterozygous and homozygous Gα<sub>o1</sub> knockout hippocampal cultures, we detected a strongly pronounced reduction in axon and dendrite length (-50% and -38%, respectively) as well as axon and dendrite arborization complexity (-75% and -72% branch nodes, respectively) in the homozygous knockout. Deletion of both splice variants Gα<sub>o1</sub> and Gα<sub>o2</sub> partially rescued the in vivo and completely reconstituted the in vitro effects, indicating an opposing functional relevance of the two Gα<sub>o</sub> splice variants for neuronal development and synaptic connectivity.</p>\",\"PeriodicalId\":16527,\"journal\":{\"name\":\"Journal of Neurochemistry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-10-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neurochemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/jnc.16248\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neurochemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/jnc.16248","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Gαo1 and Gαo1/Gαo2 deletion differentially affect hippocampal mossy fiber tract anatomy and neuronal morphogenesis.
The heterotrimeric G-protein αo subunit is ubiquitously expressed in the CNS as two splice variants Gαo1 and Gαo2, regulating various brain functions. Here, we investigated the effect of single Gαo1, Gαo2, and double Gαo1/2 knockout on the postnatal development of the murine mossy fiber tract, a central pathway of the hippocampal connectivity circuit. The size of the hippocampal synaptic termination fields covered by mossy fiber boutons together with various fiber length parameters of the tract was analyzed by immunohistochemical staining of the vesicular Zinc transporter 3 (ZnT3) or Synaptoporin at postnatal days 2, 4, 8, 12, 16, and in the adult. Ultimately, Gαo1 knockout resulted in a reduced developmental growth of synaptic mossy fiber terminal fields by 37% in the adult Stratum lucidum and by 30% in the total mossy fiber tract size. Other morphological parameters such as projection length of the infrapyramidal bundle of the tract were increased (+52% in Gαo1-/- mice). In contrast, Gαo2 knockout had no effects on the mossy fiber tract. Moreover, by using primary heterozygous and homozygous Gαo1 knockout hippocampal cultures, we detected a strongly pronounced reduction in axon and dendrite length (-50% and -38%, respectively) as well as axon and dendrite arborization complexity (-75% and -72% branch nodes, respectively) in the homozygous knockout. Deletion of both splice variants Gαo1 and Gαo2 partially rescued the in vivo and completely reconstituted the in vitro effects, indicating an opposing functional relevance of the two Gαo splice variants for neuronal development and synaptic connectivity.
期刊介绍:
Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.