Compensatory molecular and functional mechanisms in nervous system of the Grm1crv4 mouse lacking the mGlu1 receptor: A model for motor coordination deficits

Pia Irene Anna Rossi, Ilaria Musante, Maria Summa, Anna Pittaluga, Laura Emionite, Masami Ikehata, Maria Pia Rastaldi, Roberto Ravazzolo, Aldamaria Puliti

Research output: Contribution to journalArticle

Abstract

The metabotropic glutamate type 1 (mGlu1) and type 5 (mGlu5) receptors, the only members of group I mGlu receptors, are implicated in synaptic plasticity and mechanisms of feedback control of glutamate release. They exhibit nearly complementary distributions throughout the central nervous system, well evident in the cerebellum, where mGlu1 receptor is most intensely expressed while mGlu5 receptor is not. Despite their different distribution, they show a similar subcellular localization and use common transducing pathways. We recently described the Grm1crv4 mouse with motor coordination deficits and renal anomalies caused by a spontaneous mutation inactivating the mGlu1 receptor. To define the neuropathological mechanisms in these mice, we evaluated expression and function of the mGlu5 receptor in cerebral and cerebellar cortices. Western blot and immunofluorescence analyses showed mGlu5 receptor overexpression. Quantitative reverse transcriptase-polymerase chain reaction results indicated that the up-regulation is already evident at RNA level. Functional studies confirmed an enhanced glutamate release from cortical cerebral and cerebellar synaptosomes when compared with wild-type that is abolished by the mGlu5 receptor-specific inhibitor, 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP). Finally, acute MPEP treatment of Grm1 crv4/crv4 mice induced an evident although incomplete improvement of motor coordination, suggesting that mGlu5 receptors enhanced activity worsens, instead of improving, the motor-coordination defects in the Grm1 crv4/crv4 mice.

Original languageEnglish
Pages (from-to)2179-2189
Number of pages11
JournalCerebral Cortex
Volume23
Issue number9
DOIs
Publication statusPublished - Sep 2013

Keywords

  • evoked-glutamate release
  • Grm1 mouse
  • mGlu1 receptor
  • mGlu5 receptor
  • mouse cortex

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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