Effects of the Genetic Depletion of Polysialyltransferases on the Structure and Connectivity of Interneurons in the Adult Prefrontal Cortex
Polysialic acid (polySia) is a complex sugar that in the nervous system appears mainly as a posttranslational modification of the neural cell adhesion molecule (NCAM). PolySia plays important roles during brain development, but also in its plasticity during adulthood. Two polysialyltransferases (pol...
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Neuroanatomy |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnana.2019.00006/full |
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| author | Yasmina Curto Julia Alcaide Iris Röckle Herbert Hildebrandt Juan Nacher Juan Nacher Juan Nacher |
| author_facet | Yasmina Curto Julia Alcaide Iris Röckle Herbert Hildebrandt Juan Nacher Juan Nacher Juan Nacher |
| author_sort | Yasmina Curto |
| collection | DOAJ |
| description | Polysialic acid (polySia) is a complex sugar that in the nervous system appears mainly as a posttranslational modification of the neural cell adhesion molecule (NCAM). PolySia plays important roles during brain development, but also in its plasticity during adulthood. Two polysialyltransferases (polyST), ST8SIA2 and ST8SIA4, are involved in the synthesis and attachment of polySia. Both polyST are relevant for developmental migration of cortical interneurons and their establishment in the prefrontal cortex (PFC). In contrast, only ST8SIA4 appears to be important for the structural plasticity of a subpopulation of cortical interneurons in the adult. Interestingly, ST8SIA2 and NCAM are candidate genes for schizophrenia, a disorder in which interneuronal circuits are altered. However, there is still no data on the effects of polyST depletion on the dendritic structure or the connectivity of cortical interneurons. Here, we studied the contribution of each polyST on these parameters in the medial PFC (mPFC) of polyST knock-out mice with GAD67-GFP-labeled interneurons. Genetic depletion of ST8SIA4, but not ST8SIA2, resulted in a decrease in the complexity of the dendritic arbor of interneurons. In contrast, ablation of either of the two polyST induced a decrease in the density of parvalbumin (PV) expressing perisomatic puncta on pyramidal neurons. Thus, the depletion of each polyST results in similar impairments of not only developmental migration but also efferent synaptic connectivity of interneurons. In contrast, the loss of ST8SIA4 has a unique effect on dendritic structure, hence on afferent connectivity, suggesting differential and independent contributions of each polyST to neuritogenesis and synaptogenesis. |
| first_indexed | 2024-12-19T03:59:46Z |
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| id | doaj.art-4bfd2aba903d44bda8bc873e96436478 |
| institution | Directory Open Access Journal |
| issn | 1662-5129 |
| language | English |
| last_indexed | 2024-12-19T03:59:46Z |
| publishDate | 2019-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroanatomy |
| spelling | doaj.art-4bfd2aba903d44bda8bc873e964364782022-12-21T20:36:42ZengFrontiers Media S.A.Frontiers in Neuroanatomy1662-51292019-02-011310.3389/fnana.2019.00006432254Effects of the Genetic Depletion of Polysialyltransferases on the Structure and Connectivity of Interneurons in the Adult Prefrontal CortexYasmina Curto0Julia Alcaide1Iris Röckle2Herbert Hildebrandt3Juan Nacher4Juan Nacher5Juan Nacher6Neurobiology Unit, Department of Cell Biology, Interdisciplinary Research Structure for Biotechnology and Biomedicine (BIOTECMED), Universitat de València, Valencia, SpainNeurobiology Unit, Department of Cell Biology, Interdisciplinary Research Structure for Biotechnology and Biomedicine (BIOTECMED), Universitat de València, Valencia, SpainInstitute of Clinical Biochemistry, Hannover Medical School, Hannover, GermanyInstitute of Clinical Biochemistry, Hannover Medical School, Hannover, GermanyNeurobiology Unit, Department of Cell Biology, Interdisciplinary Research Structure for Biotechnology and Biomedicine (BIOTECMED), Universitat de València, Valencia, SpainCentro de Investigación Biomédica en Red de Salud Mental (CIBERSAM): Spanish National Network for Research in Mental Health, Madrid, SpainFundación Investigación Hospital Clínico de Valencia, INCLIVA, Valencia, SpainPolysialic acid (polySia) is a complex sugar that in the nervous system appears mainly as a posttranslational modification of the neural cell adhesion molecule (NCAM). PolySia plays important roles during brain development, but also in its plasticity during adulthood. Two polysialyltransferases (polyST), ST8SIA2 and ST8SIA4, are involved in the synthesis and attachment of polySia. Both polyST are relevant for developmental migration of cortical interneurons and their establishment in the prefrontal cortex (PFC). In contrast, only ST8SIA4 appears to be important for the structural plasticity of a subpopulation of cortical interneurons in the adult. Interestingly, ST8SIA2 and NCAM are candidate genes for schizophrenia, a disorder in which interneuronal circuits are altered. However, there is still no data on the effects of polyST depletion on the dendritic structure or the connectivity of cortical interneurons. Here, we studied the contribution of each polyST on these parameters in the medial PFC (mPFC) of polyST knock-out mice with GAD67-GFP-labeled interneurons. Genetic depletion of ST8SIA4, but not ST8SIA2, resulted in a decrease in the complexity of the dendritic arbor of interneurons. In contrast, ablation of either of the two polyST induced a decrease in the density of parvalbumin (PV) expressing perisomatic puncta on pyramidal neurons. Thus, the depletion of each polyST results in similar impairments of not only developmental migration but also efferent synaptic connectivity of interneurons. In contrast, the loss of ST8SIA4 has a unique effect on dendritic structure, hence on afferent connectivity, suggesting differential and independent contributions of each polyST to neuritogenesis and synaptogenesis.https://www.frontiersin.org/article/10.3389/fnana.2019.00006/fullpolysialic acid (polysia)interneuronbasket cellpolysialyltransferasesprefrontal cortexdendritic arborization |
| spellingShingle | Yasmina Curto Julia Alcaide Iris Röckle Herbert Hildebrandt Juan Nacher Juan Nacher Juan Nacher Effects of the Genetic Depletion of Polysialyltransferases on the Structure and Connectivity of Interneurons in the Adult Prefrontal Cortex Frontiers in Neuroanatomy polysialic acid (polysia) interneuron basket cell polysialyltransferases prefrontal cortex dendritic arborization |
| title | Effects of the Genetic Depletion of Polysialyltransferases on the Structure and Connectivity of Interneurons in the Adult Prefrontal Cortex |
| title_full | Effects of the Genetic Depletion of Polysialyltransferases on the Structure and Connectivity of Interneurons in the Adult Prefrontal Cortex |
| title_fullStr | Effects of the Genetic Depletion of Polysialyltransferases on the Structure and Connectivity of Interneurons in the Adult Prefrontal Cortex |
| title_full_unstemmed | Effects of the Genetic Depletion of Polysialyltransferases on the Structure and Connectivity of Interneurons in the Adult Prefrontal Cortex |
| title_short | Effects of the Genetic Depletion of Polysialyltransferases on the Structure and Connectivity of Interneurons in the Adult Prefrontal Cortex |
| title_sort | effects of the genetic depletion of polysialyltransferases on the structure and connectivity of interneurons in the adult prefrontal cortex |
| topic | polysialic acid (polysia) interneuron basket cell polysialyltransferases prefrontal cortex dendritic arborization |
| url | https://www.frontiersin.org/article/10.3389/fnana.2019.00006/full |
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