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Auteur Masahiro FUJITA |
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Is metabotropic glutamate receptor 5 upregulated in prefrontal cortex in fragile X syndrome? / Talakad LOHITH in Molecular Autism, (May 2013)
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Titre : Is metabotropic glutamate receptor 5 upregulated in prefrontal cortex in fragile X syndrome? Type de document : Texte imprimé et/ou numérique Auteurs : Talakad LOHITH, Auteur ; Emily OSTERWEIL, Auteur ; Masahiro FUJITA, Auteur ; Kimberly JENKO, Auteur ; Mark F. BEAR, Auteur ; Robert INNIS, Auteur Année de publication : 2013 Article en page(s) : 8 p. Langues : Anglais (eng) Mots-clés : Fragile X mental retardation protein Fragile X syndrome Glutamate receptor mGluR5 Receptor density Receptor expression Index. décimale : PER Périodiques Résumé : BACKGROUND:Fragile X syndrome (FXS) is a common inherited form of intellectual disability caused by loss of function of the fragile X mental retardation protein. Recent animal studies suggest that upregulated downstream signaling by metabotropic glutamate receptor 5 (mGluR5) might be an important mechanism for cognitive and behavioral abnormalities associated with FXS. However, mGluR5 density in human FXS remains unknown.METHODS:Receptor binding and protein expression were measured in the postmortem prefrontal cortex of 14 FXS patients or carriers and 17 age- and sex-matched control subjects without neurological disorders. In-vitro binding assays were performed using [3H]-labeled 3-methoxy-5-pyridin-2-ylethynylpyridine (MPEPy), a selective and high-affinity negative allosteric modulator of mGluR5, to measure receptor density and the radioligand's dissociation constant, which is inversely proportional to affinity. Immunoblotting was also performed, to measure mGluR5 protein expression.RESULTS:The mGluR5 density increased with marginal significance (+16%; P = 0.058) in the prefrontal cortex of FXS patients or carriers compared with matched healthy controls. No significant change in dissociation constant (-4%; P = 0.293) was observed. Immunoblotting found a significant elevation (+32%; P = 0.048) in mGluR5 protein expression.CONCLUSIONS:Both mGluR5 binding density and protein expression were increased in the brains of FXS patients or carriers, but only expression was significantly different, which could be because of the small sample size and moderate variability. Another important caveat is that the effects of psychotropic medications on mGluR5 expression are largely unknown. Future in-vivo measurement of mGluR5 with positron emission tomography might characterize the role of this receptor in the pathophysiology of FXS and facilitate trials of mGluR5-oriented treatments for this disorder. En ligne : http://dx.doi.org/10.1186/2040-2392-4-15 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202
in Molecular Autism > (May 2013) . - 8 p.[article] Is metabotropic glutamate receptor 5 upregulated in prefrontal cortex in fragile X syndrome? [Texte imprimé et/ou numérique] / Talakad LOHITH, Auteur ; Emily OSTERWEIL, Auteur ; Masahiro FUJITA, Auteur ; Kimberly JENKO, Auteur ; Mark F. BEAR, Auteur ; Robert INNIS, Auteur . - 2013 . - 8 p.
Langues : Anglais (eng)
in Molecular Autism > (May 2013) . - 8 p.
Mots-clés : Fragile X mental retardation protein Fragile X syndrome Glutamate receptor mGluR5 Receptor density Receptor expression Index. décimale : PER Périodiques Résumé : BACKGROUND:Fragile X syndrome (FXS) is a common inherited form of intellectual disability caused by loss of function of the fragile X mental retardation protein. Recent animal studies suggest that upregulated downstream signaling by metabotropic glutamate receptor 5 (mGluR5) might be an important mechanism for cognitive and behavioral abnormalities associated with FXS. However, mGluR5 density in human FXS remains unknown.METHODS:Receptor binding and protein expression were measured in the postmortem prefrontal cortex of 14 FXS patients or carriers and 17 age- and sex-matched control subjects without neurological disorders. In-vitro binding assays were performed using [3H]-labeled 3-methoxy-5-pyridin-2-ylethynylpyridine (MPEPy), a selective and high-affinity negative allosteric modulator of mGluR5, to measure receptor density and the radioligand's dissociation constant, which is inversely proportional to affinity. Immunoblotting was also performed, to measure mGluR5 protein expression.RESULTS:The mGluR5 density increased with marginal significance (+16%; P = 0.058) in the prefrontal cortex of FXS patients or carriers compared with matched healthy controls. No significant change in dissociation constant (-4%; P = 0.293) was observed. Immunoblotting found a significant elevation (+32%; P = 0.048) in mGluR5 protein expression.CONCLUSIONS:Both mGluR5 binding density and protein expression were increased in the brains of FXS patients or carriers, but only expression was significantly different, which could be because of the small sample size and moderate variability. Another important caveat is that the effects of psychotropic medications on mGluR5 expression are largely unknown. Future in-vivo measurement of mGluR5 with positron emission tomography might characterize the role of this receptor in the pathophysiology of FXS and facilitate trials of mGluR5-oriented treatments for this disorder. En ligne : http://dx.doi.org/10.1186/2040-2392-4-15 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202