Related Experiment Video
Updated: May 16, 2026

Using Enzyme-based Biosensors to Measure Tonic and Phasic Glutamate in Alzheimer's Mouse Models
Published on: May 3, 2017
Inhibition of glutamate carboxypeptidase II (GCPII) activity as a treatment for cognitive impairment in multiple
Kristen A Rahn1, Crystal C Watkins, Jesse Alt
1Department of Psychiatry and Behavioral Sciences, Brain Science Institute, Johns Hopkins University, Baltimore, MD 21287, USA.
Abstract:
Half of all patients with multiple sclerosis (MS) experience cognitive impairment, for which there is no pharmacological treatment. Using magnetic resonance spectroscopy (MRS), we examined metabolic changes in the hippocampi of MS patients, compared the findings to performance on a neurocognitive test battery, and found that N-acetylaspartylglutamate (NAAG) concentration correlated with cognitive functioning. Specifically, MS patients with cognitive impairment had low hippocampal NAAG levels, whereas those with normal cognition demonstrated higher levels. We then evaluated glutamate carboxypeptidase II (GCPII) inhibitors, known to increase brain NAAG levels, on cognition in the experimental autoimmune encephalomyelitis (EAE) model of MS. Whereas GCPII inhibitor administration did not affect physical disabilities, it increased brain NAAG levels and dramatically improved learning and memory test performance compared with vehicle-treated EAE mice. These data suggest that NAAG is a unique biomarker for cognitive function in MS and that inhibition of GCPII might be a unique therapeutic strategy for recovery of cognitive function.
Related Concept Videos
Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Antiepileptic Drugs: Glutamate Antagonists
Alzheimer's Disease: Treatment
Antiepileptic Drugs: GABAergic Pathway Potentiators
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for their...
Indirect-Acting Cholinergic Agonists: Pharmacological Actions
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...