A Novel Biomarker of Neuronal Glutamate Metabolism in Nonhuman Primates Using Localized ¹H-Magnetic Resonance Spectroscopy: Development and Effects of BNC375, an α7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator.

ABSTRACT:

Background

The development of treatments for cognitive deficits associated with central nervous system disorders is currently a significant medical need. Despite the great need for such therapeutics, a significant challenge in the drug development process is the paucity of robust biomarkers to assess target modulation and guide clinical decisions. We developed a novel, translatable biomarker of neuronal glutamate metabolism, the ¹³C-glutamate+glutamine (Glx) H3:H4 labeling ratio, in nonhuman primates using localized ¹H-magnetic resonance spectroscopy combined with ¹³C-glucose infusions.

Methods

We began with numerical simulations in an established model of brain glutamate metabolism, showing that the ¹³C-Glx H3:H4 ratio should be a

SUBMITTER: Miller CO 

PROVIDER: S-EPMC8005500 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature