Letter to the EditorExistence of monomer and dimer forms of mGluR5, under reducing conditions in studies of postmortem brain in various psychiatric disorders
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Funding body agreements and policies
Funding for this study was provided by the National Institute of Child Health and Human Development (NICHD), Grant #5R01HD052074-05 and 3R01HD052074-03S1, the National Institute of Mental Health (NIMH), Grant #5R01MH086000-05 and the Ewald Bipolar Disease Research Fund (SHF). NICHD, NIMH, and the Ewald Bipolar Disease Research Fund had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper
Contributions
Both SHF and TDF wrote and edited this manuscript and approve of the final version of the manuscript.
Conflict of interest
The authors declare that they have no conflict of interest.
Acknowledgments
Grant support by National Institute of Child Health and Human Development (#5R01HD052074-01A2 and 3R01HD052074-03S1), National Institute of Mental Health (Grant #1R01MH086000-01A2), and the Ewald Bipolar Disease Research Fund to SHF are gratefully acknowledged. S.H. Fatemi is also supported by the Bernstein Endowed Chair in Adult Psychiatry.
References (10)
- et al.
Altered dimerization of metabotropic glutamate receptor 3 in schizophrenia
Biol. Psychiatry
(2007) - et al.
An increased expression of the mGlu5 receptor protein following LTP induction at the perforant path-dentate gyrus synapse in freely moving rats
Neuropharmacology
(2003) - et al.
Metabotropic glutamate receptor 5 binding and protein expression in schizophrenia and following antipsychotic drug treatment
Schizophr. Res.
(2013) - et al.
Metabotropic glutamate receptor 5 is a disulfide-linked dimer
J. Biol. Chem.
(1996) - et al.
Distinct roles of metabotropic glutamate receptor dimerization in agonist activation and G-protein coupling
Proc. Natl. Acad. Sci. U. S. A.
(2012)
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2020, Neuroscience and Biobehavioral ReviewsCitation Excerpt :Prenatal exposures to different insults induce alterations in several biological systems leading to an increased vulnerability of developing SZ and ASD later in life; moreover, as different insults lead to alterations in common biological systems, this could also explain why some of the symptoms are shared across NDDs. Several biological systems have been proposed to play a pivotal role, including: i) neurotransmitter systems (Chiocchetti et al., 2014; Coyle, 2012; Deidda et al., 2014; Fatemi and Folsom, 2014; Kantrowitz and Javitt, 2012; Karam et al., 2010; Rojas, 2014; Steiner et al., 2013), ii) inflammation (McDougle et al., 2015; Meyer, 2013; Potvin et al., 2008; Saetre et al., 2007; van Berckel et al., 2008), and iii) redox signaling (Clay et al., 2011; Do et al., 2009; Gysin et al., 2011; Porokhovnik et al., 2015). A deregulation in all these pathways and their reciprocal interactions have been proposed to represent one “central hub” underlying the development and the onset of both SZ and ASD (Steullet et al., 2017, 2016).
GABA receptor subunit distribution and FMRP-mGluR5 signaling abnormalities in the cerebellum of subjects with schizophrenia, mood disorders, and autism
2015, Schizophrenia ResearchCitation Excerpt :Similarly, three groups measured mRNA levels of mGluR5 in schizophrenia and did not report any changes in the hippocampus, thalamus, BA9, or BA42 (Ohnuma et al., 2000; Richardson-Burns et al., 2000; Volk et al., 2010). Thus as recently discussed (Fatemi and Folsom, 2014), measurements of both monomer and dimer forms of mGluR5 by western blotting are a requirement for accurate measurement of any change in postmortem studies. In contrast, a positron emission tomography (PET) study found reduced expression in mGluR5 in the PFC, cingulate cortex (CC), insula, thalamus, and hippocampus of subjects with depression while western blotting found reduction in PFC (Deschwanden et al., 2011) (Table 6).
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