NAAG Peptidase Inhibitors Act via mGluR3: Animal Models of Memory, Alzheimer's, and Ethanol Intoxication.

NAAG Peptidase Inhibitors Act via mGluR3: Animal Models of Memory, Alzheimer's, and Ethanol Intoxication. Neurochem Res. 2017 Mar 11;: Authors: Olszewski RT, Janczura KJ, Bzdega T, Der EK, Venzor F, O'Rourke B, Hark TJ, Craddock KE, Balasubramanian S, Moussa C, Neale JH Abstract Glutamate carboxypeptidase II (GCPII) inactivates the peptide neurotransmitter N-acetylaspartylglutamate (NAAG) following synaptic release. Inhibitors of GCPII increase extracellular NAAG levels and are efficacious in animal models of clinical disorders via NAAG activation of a group II metabotropic glutamate receptor. mGluR2 and mGluR3 knock-out (ko) mice were used to test the hypothesis that mGluR3 mediates the activity of GCPII inhibitors ZJ43 and 2-PMPA in animal models of memory and memory loss. Short- (1.5 h) and long- (24 h) term novel object recognition tests were used to assess memory. Treatment with ZJ43 or 2-PMPA prior to acquisition trials increased long-term memory in mGluR2, but not mGluR3, ko mice. Nine month-old triple transgenic Alzheimer's disease model mice exhibited impaired short-term novel object recognition memory that was rescued by treatment with a NAAG peptidase inhibitor. NAAG peptidase inhibitors and the group II mGluR agonist, LY354740, reversed the short-term memory deficit induced by acute ethanol administration in wild type mice. 2-PMPA also moderated the effect of ethanol on short-term memory in mGluR2 ko mice but failed to ...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research