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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 mGluR1 alpha
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,
mGluR1a 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 mGluR1a
(-50-56%). Perinatal PCP treatment also reduced mGluR1a 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.
