دورية أكاديمية
Differential Adulthood Onset mGlu5 Signaling Saves Prefrontal Function in the Fragile X Mouse.
| العنوان: | Differential Adulthood Onset mGlu5 Signaling Saves Prefrontal Function in the Fragile X Mouse. |
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| المؤلفون: | Martin HGS; INSERM U901, Marseille 13009, France.; INMED, Marseille 13009, France.; Université de Aix-Marseille, UMR S901, Marseille 13009, France., Lassalle O; INSERM U901, Marseille 13009, France.; INMED, Marseille 13009, France.; Université de Aix-Marseille, UMR S901, Marseille 13009, France., Manzoni OJ; INSERM U901, Marseille 13009, France.; INMED, Marseille 13009, France.; Université de Aix-Marseille, UMR S901, Marseille 13009, France. |
| المصدر: | Cerebral cortex (New York, N.Y. : 1991) [Cereb Cortex] 2017 Dec 01; Vol. 27 (12), pp. 5592-5602. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 9110718 Publication Model: Print Cited Medium: Internet ISSN: 1460-2199 (Electronic) Linking ISSN: 10473211 NLM ISO Abbreviation: Cereb Cortex Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Oxford University Press, c1991- |
| مواضيع طبية MeSH: | Fragile X Syndrome/*metabolism , Long-Term Synaptic Depression/*physiology , Prefrontal Cortex/*growth & development , Prefrontal Cortex/*metabolism , Receptor, Metabotropic Glutamate 5/*metabolism, Aging/metabolism ; Animals ; Endocannabinoids/metabolism ; Endophenotypes ; Excitatory Postsynaptic Potentials/physiology ; Fragile X Mental Retardation Protein/genetics ; Fragile X Mental Retardation Protein/metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Patch-Clamp Techniques ; Recovery of Function/physiology ; Signal Transduction ; Tissue Culture Techniques |
| مستخلص: | The final maturation of the prefrontal cortex (PFC) continues into early adulthood and is delayed compared with other forebrain structures. However, how these late onset changes in the PFC relate to neurodevelopment disorders is poorly understood. Fragile X syndrome (FXS) is a prevalent neurogenetic disorder linked to deficits in PFC function. mGlu5 is an important molecular hub in the etiology of FXS. Thus we have examined changes in mGlu5 function in the PFC in a mouse model of FXS (Fmr1 knockout) during early adulthood and subsequent maturity. An unusual endophenotype was identified; during early adulthood (2-month-old) Fmr1 knockout mice show a severe deficit in mGlu5 dependent eCB synaptic plasticity; however, in 1-year-old this deficit self rectifies. This adulthood onset correction in mGlu5 function is linked to an engagement of TRPV1 receptors in 1-year-old mice. In 2-month-old Fmr1 knockout mice, mGlu5 mediated synaptic plasticity could be recovered with eCB system targeted drugs, but also by direct enhancement of mGlu5 function with a positive allosteric modulator. These results point to further refinements to the role of mGlu5 in FXS. Furthermore our findings suggest when studying neurodevelopmental disorders with a significant PFC phenotype consideration of late onset changes may be important. (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.) |
| فهرسة مساهمة: | Keywords: LTD; endocannabinoid; fragile X; mGlu5 receptor; synaptic plasticity |
| المشرفين على المادة: | 0 (Endocannabinoids) 0 (Fmr1 protein, mouse) 0 (Grm5 protein, mouse) 0 (Receptor, Metabotropic Glutamate 5) 139135-51-6 (Fragile X Mental Retardation Protein) |
| تواريخ الأحداث: | Date Created: 20161101 Date Completed: 20180703 Latest Revision: 20181018 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1093/cercor/bhw328 |
| PMID: | 27797833 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1460-2199 |
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| DOI: | 10.1093/cercor/bhw328 |