Neurodevelopmental expression profile of dimeric and monomeric group 1 mGluRs: Relevance to Schizophrenia pathogenesis and treatment

Journal article


Lum, Jeremy S., Fernandez, Francesca, Matosin, Natalie, Andrews, Jessica L., Huang, Xu-Feng, Ooi, Lezanne and Newell, Kelly A.. (2016) Neurodevelopmental expression profile of dimeric and monomeric group 1 mGluRs: Relevance to Schizophrenia pathogenesis and treatment. Scientific Reports. 6, pp. 1 - 10. https://doi.org/10.1038/srep34391
AuthorsLum, Jeremy S., Fernandez, Francesca, Matosin, Natalie, Andrews, Jessica L., Huang, Xu-Feng, Ooi, Lezanne and Newell, Kelly A.
Abstract

Abstract Group 1 metabotropic glutamate receptors (mGluR1/mGluR5) play an integral role in neurodevelopment and are implicated in psychiatric disorders, such as schizophrenia. mGluR1 and mGluR5 are expressed as homodimers, which is important for their functionality and pharmacology. We examined the protein expression of dimeric and monomeric mGluR1α and mGluR5 in the prefrontal cortex (PFC) and hippocampus throughout development (juvenile/adolescence/adulthood) and in the perinatal phencyclidine (PCP) model of schizophrenia. Under control conditions, mGluR1α dimer expression increased between juvenile and adolescence (209–328%), while monomeric levels remained consistent. Dimeric mGluR5 was steadily expressed across all time points; monomeric mGluR5 was present in juveniles, dramatically declining at adolescence and adulthood (−97–99%). The mGluR regulators, Homer 1b/c and Norbin, significantly increased with age in the PFC and hippocampus. Perinatal PCP treatment significantly increased juvenile dimeric mGluR5 levels in the PFC and hippocampus (37–50%) but decreased hippocampal mGluR1α (−50–56%). Perinatal PCP treatment also reduced mGluR1α dimer levels in the PFC at adulthood (−31%). These results suggest that Group 1 mGluRs have distinct dimeric and monomeric neurodevelopmental patterns, which may impact their pharmacological profiles at specific ages. Perinatal PCP treatment disrupted the early expression of Group 1 mGluRs which may underlie neurodevelopmental alterations observed in this model.

Keywordsdevelopment of the nervous system; neurochemistry; schizophrenia
Year2016
JournalScientific Reports
Journal citation6, pp. 1 - 10
PublisherNature Publishing Group
ISSN2045-2322
Digital Object Identifier (DOI)https://doi.org/10.1038/srep34391
Scopus EID2-s2.0-84990913737
Open accessOpen access
Page range1 - 10
Research GroupSchool of Behavioural and Health Sciences
Publisher's version
License
Place of publicationUnited Kingdom
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