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Hippocampal Excitatory Synaptic Transmission and Plasticity Are Differentially Altered during Postnatal Development by Loss of the X-Linked Intellectual Disability Protein Oligophrenin-1
Oligophrenin-1 (OPHN1) is a Rho-GTPase-activating protein (RhoGAP), whose mutations are associated with X-linked intellectual disability (XLID). OPHN1 is enriched at the synapse in both pre- and postsynaptic compartments, where it regulates the RhoA/ROCK/MLC2 signaling pathway, playing a critical ro...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105236/ https://www.ncbi.nlm.nih.gov/pubmed/35563851 http://dx.doi.org/10.3390/cells11091545 |
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author | Cresto, Noemie Lebrun, Nicolas Dumont, Florent Letourneur, Franck Billuart, Pierre Rouach, Nathalie |
author_facet | Cresto, Noemie Lebrun, Nicolas Dumont, Florent Letourneur, Franck Billuart, Pierre Rouach, Nathalie |
author_sort | Cresto, Noemie |
collection | PubMed |
description | Oligophrenin-1 (OPHN1) is a Rho-GTPase-activating protein (RhoGAP), whose mutations are associated with X-linked intellectual disability (XLID). OPHN1 is enriched at the synapse in both pre- and postsynaptic compartments, where it regulates the RhoA/ROCK/MLC2 signaling pathway, playing a critical role in cytoskeleton remodeling and vesicle recycling. Ophn1 knockout (KO) adult mice display some behavioral deficits in multiple tasks, reminiscent of some symptoms in the human pathology. We also previously reported a reduction in dendritic spine density in the adult hippocampus of KO mice. Yet the nature of the deficits occurring in these mice during postnatal development remains elusive. Here, we show that juvenile KO mice present normal basal synaptic transmission, but altered synaptic plasticity, with a selective impairment in long-term depression, but no change in long-term potentiation. This contrasts with the functional deficits that these mice display at the adult stage, as we found that both basal synaptic transmission and long-term potentiation are reduced at later stages, due to presynaptic alterations. In addition, the number of excitatory synapses in adult is increased, suggesting some unsuccessful compensation. Altogether, these results suggest that OPHN1 function at synapses is differentially affected during maturation of the brain, which provides some therapeutic opportunities for early intervention. |
format | Online Article Text |
id | pubmed-9105236 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91052362022-05-14 Hippocampal Excitatory Synaptic Transmission and Plasticity Are Differentially Altered during Postnatal Development by Loss of the X-Linked Intellectual Disability Protein Oligophrenin-1 Cresto, Noemie Lebrun, Nicolas Dumont, Florent Letourneur, Franck Billuart, Pierre Rouach, Nathalie Cells Article Oligophrenin-1 (OPHN1) is a Rho-GTPase-activating protein (RhoGAP), whose mutations are associated with X-linked intellectual disability (XLID). OPHN1 is enriched at the synapse in both pre- and postsynaptic compartments, where it regulates the RhoA/ROCK/MLC2 signaling pathway, playing a critical role in cytoskeleton remodeling and vesicle recycling. Ophn1 knockout (KO) adult mice display some behavioral deficits in multiple tasks, reminiscent of some symptoms in the human pathology. We also previously reported a reduction in dendritic spine density in the adult hippocampus of KO mice. Yet the nature of the deficits occurring in these mice during postnatal development remains elusive. Here, we show that juvenile KO mice present normal basal synaptic transmission, but altered synaptic plasticity, with a selective impairment in long-term depression, but no change in long-term potentiation. This contrasts with the functional deficits that these mice display at the adult stage, as we found that both basal synaptic transmission and long-term potentiation are reduced at later stages, due to presynaptic alterations. In addition, the number of excitatory synapses in adult is increased, suggesting some unsuccessful compensation. Altogether, these results suggest that OPHN1 function at synapses is differentially affected during maturation of the brain, which provides some therapeutic opportunities for early intervention. MDPI 2022-05-05 /pmc/articles/PMC9105236/ /pubmed/35563851 http://dx.doi.org/10.3390/cells11091545 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cresto, Noemie Lebrun, Nicolas Dumont, Florent Letourneur, Franck Billuart, Pierre Rouach, Nathalie Hippocampal Excitatory Synaptic Transmission and Plasticity Are Differentially Altered during Postnatal Development by Loss of the X-Linked Intellectual Disability Protein Oligophrenin-1 |
title | Hippocampal Excitatory Synaptic Transmission and Plasticity Are Differentially Altered during Postnatal Development by Loss of the X-Linked Intellectual Disability Protein Oligophrenin-1 |
title_full | Hippocampal Excitatory Synaptic Transmission and Plasticity Are Differentially Altered during Postnatal Development by Loss of the X-Linked Intellectual Disability Protein Oligophrenin-1 |
title_fullStr | Hippocampal Excitatory Synaptic Transmission and Plasticity Are Differentially Altered during Postnatal Development by Loss of the X-Linked Intellectual Disability Protein Oligophrenin-1 |
title_full_unstemmed | Hippocampal Excitatory Synaptic Transmission and Plasticity Are Differentially Altered during Postnatal Development by Loss of the X-Linked Intellectual Disability Protein Oligophrenin-1 |
title_short | Hippocampal Excitatory Synaptic Transmission and Plasticity Are Differentially Altered during Postnatal Development by Loss of the X-Linked Intellectual Disability Protein Oligophrenin-1 |
title_sort | hippocampal excitatory synaptic transmission and plasticity are differentially altered during postnatal development by loss of the x-linked intellectual disability protein oligophrenin-1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105236/ https://www.ncbi.nlm.nih.gov/pubmed/35563851 http://dx.doi.org/10.3390/cells11091545 |
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