Targeting mGlu5 Metabotropic Glutamate Receptors in the Treatment of Cognitive Dysfunction in a Mouse Model of Phenylketonuria.

ABSTRACT: We studied group-I metabotropic glutamate (mGlu) receptors in Pahenu2 (ENU2) mice, which mimic the genetics and neurobiology of human phenylketonuria (PKU), a metabolic disorder characterized, if untreated, by autism, and intellectual disability (ID). Male ENU2 mice showed increased mGlu5 receptor protein levels in the hippocampus and corpus striatum (but not in the prefrontal cortex) whereas the transcript of the mGlu5 receptor was unchanged. No changes in mGlu1 receptor mRNA and protein levels were found in any of the three brain regions of ENU2 mice. We extended the analysis to Homer proteins, which act as scaffolds by linking mGlu1 and mGlu5 receptors to effector proteins. Expression of the long isoforms of Homer was significantly reduced in the hippocampus of ENU2 mice, whereas levels

SUBMITTER: Nardecchia F 

PROVIDER: S-EPMC5864888 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature