toggle visibility Search & Display Options

Select All    Deselect All
 |   | 
  Record Links
Author Achuta, V.S.; Grym, H.; Putkonen, N.; Louhivuori, V.; Karkkainen, V.; Koistinaho, J.; Roybon, L.; Castren, M.L. url  doi
  Title Metabotropic glutamate receptor 5 responses dictate differentiation of neural progenitors to NMDA-responsive cells in fragile X syndrome Type Journal Article
  Year 2016 Publication Developmental Neurobiology Abbreviated Journal Dev Neurobiol  
  Volume Issue Pages  
  Keywords (up) 2-methyl-6-(phenylethynyl)-pyridine; fragile X syndrome; glutamatergic neurons; induced pluripotent stem cells; metabotropic glutamate receptor 5  
  Abstract Disrupted metabotropic glutamate receptor 5 (mGluR5) signaling is implicated in many neuropsychiatric disorders, including autism spectrum disorder, found in fragile X syndrome (FXS). Here we report that intracellular calcium responses to the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) are augmented, and calcium-dependent mGluR5-mediated mechanisms alter the differentiation of neural progenitors in neurospheres derived from human induced pluripotent FXS stem cells and the brains of mouse model of FXS. Treatment with the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) prevents an abnormal clustering of DHPG-responsive cells that are responsive to activation of ionotropic receptors in mouse FXS neurospheres. MPEP also corrects morphological defects of differentiated cells and enhanced migration of neuron-like cells in mouse FXS neurospheres. Unlike in mouse neurospheres, MPEP increases the differentiation of DHPG-responsive radial glial cells as well as the subpopulation of cells responsive to both DHPG and activation of ionotropic receptors in human neurospheres. However, MPEP normalizes the FXS-specific increase in the differentiation of cells responsive only to N-methyl-d-aspartate (NMDA) present in human neurospheres. Exposure to MPEP prevents the accumulation of intermediate basal progenitors in embryonic FXS mouse brain suggesting that rescue effects of GluR5 antagonist are progenitor type-dependent and species-specific differences of basal progenitors may modify effects of MPEP on the cortical development. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol, 2016.  
  Address Autism Foundation, Kuortaneenkatu 7B, Helsinki, FI-00520, Finland  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1932-8451 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27411166 Approved no  
  Call Number ref @ user @ Serial 95938  
Permanent link to this record
Select All    Deselect All
 |   | 

Save Citations:
Export Records: