Engineering Commons^™

Reducing Brain Kynurenic Acid Synthesis Precludes Kynurenine-Induced Sleep Disturbances, Katherine M. Rentschler, Snezana Milosavljevic, Annalisa M. Baratta, Courtney J. Wright, Maria V. Piroli, Zachary Tentor, Homayoun Valafar, Christian O'Reilly, Ana Pocivavsek

Publications

Patients with neurocognitive disorders often battle sleep disturbances. Kynurenic acid is a tryptophan metabolite of the kynurenine pathway implicated in the pathology of these illnesses. Modest increases in kynurenic acid, an antagonist at glutamatergic and cholinergic receptors, result in cognitive impairments and sleep dysfunction. We explored the hypothesis that inhibition of the kynurenic acid synthesising enzyme, kynurenine aminotransferase II, may alleviate sleep disturbances. At the start of the light phase, adult male and female Wistar rats received systemic injections of either: (i) vehicle; (ii) kynurenine (100 mg kg−1; i.p.); (iii) the kynurenine aminotransferase II inhibitor, PF-04859989 (30 mg kg−1; s.c.); …