Education

B.S. Psychology, Duke University

Ph.D. Neuroscience, Georgetown University

Postdoctoral: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine

Research

My research laboratory focuses extensively on the underlying molecular mechanisms of sleep dysfunction. Poor sleep quality is associated with mental illness and impairments in cognitive function. My research strives to unravel molecular underpinnings between sleep disturbances, cognitive impairments and introduce new therapeutic approaches to alleviate these outcomes. The major focus of my program is on the neurobiology of kynurenic acid, a neuroinhibitory product of the kynurenine pathway of tryptophan degradation in sleep neurobiology. Specifically, my research has advanced our understanding of the relationship between tryptophan metabolism and kynurenic acid formation, sleep, and cognitive deficits across the lifespan. We are studying these relationships during neurodevelopment, adolescence, adulthood, and during normal aging.

Role of kynurenic acid in cognition
Metabolites of the kynurenine pathway of tryptophan degradation, including kynurenic acid and quinolinic acid, are increasingly understood to play major roles in nervous system development, function as neuromodulators, and participate causally in pathological states, including severe mental illness (schizophrenia, bipolar disorder).  Targeted inhibition of kynurenic acid formation is being investigated as a therapeutic approach to overcoming cognitive impairments.

Kynurenic acid as a molecular link between sleep and cognition
Only about 5% of dietary tryptophan, which is elevated in serum and brain after prolonged wakefulness and implicated in modulating sleep, is degraded to serotonin and melatonin.  The vast majority of tryptophan is metabolized in the kynurenine pathway, which is also responsible for the neosynthesis of kynurenic acid.  However, the direct relationship between sleep and kynurenine pathway metabolism remains elusive.  We are conducting in vivo preclinical studies to decipher the role of kynurenic acid in modulating sleep behavior and neurocognitive outcomes.

Recent Publications

Pocivavsek A, Schwarcz R, Erhardt S. Neuroactive kynurenines as pharmacological targets: New experimental tools and exciting therapeutic opportunities. Pharmacol Rev. 2024 Sep 20:PHARMREV-AR-2020-000239. doi: 10.1124/pharmrev.124.000239. Pubmed PMID: 39304346

Rentschler KM, Milosavljevic S, Baratta AM, Wright CJ, Piroli MV, Wagner NTJ, Valafar H. O’Reilly C. Pocivavsek A. Reducing brain kynurenic acid synthesis precludes kynurenine-induced sleep disturbances. Journal of Sleep Research. 2023 Sept 7;e14038. Doi: 10.1111/jsr.14038. Pubmed PMID: 37678806 

Pocivavsek A, Erhardt S. Kynurenic acid: translational perspectives of a therapeutically targetable gliotransmitter. Neuropsychopharmacology. 2023. Doi: 10.1038/s41386-023-01681-6. Pubmed PMID: 37500723.

Milosavljevic S, Smith A, Wright CJ, Valafar H, Pocivavsek A. Kynurenine aminotransferase II inhibition promotes sleep and rescues impairments induced by neurodevelopmental insult. Translational Psychiatry. 2023 Mar 31;13:106; Doi: 10.1038/s41398-023-02399-1. PubMed PMID: 37002202. 

Rentschler KM, Baratta AM, Ditty AL, Wagner NTJ, Wright CJ, Milosavljevic S, Mong JA, Pocivavsek A. Prenatal Kynurenine Elevation Elicits Sex-Dependent Changes in Sleep and Arousal During Adulthood: Implications for Psychotic Disorders. Schizophr Bull. 2021 Aug 21;47(5):1320-1330. doi: 10.1093/schbul/sbab029. PubMed PMID: 33823027; PubMed Central PMCID: PMC8379538.

Wright CJ, Rentschler KM, Wagner NTJ, Lewis AM, Beggiato S, Pocivavsek A. Time of Day-Dependent Alterations in Hippocampal Kynurenic Acid, Glutamate, and GABA in Adult Rats Exposed to Elevated Kynurenic Acid During Neurodevelopment. Front Psychiatry. 2021;12:734984. PubMed PMID: 34603109; PubMed Central PMCID: PMC8484637.

Buck SA, Baratta AM, Pocivavsek A. Exposure to elevated embryonic kynurenine in rats: Sex-dependent learning and memory impairments in adult offspring. Neurobiol Learn Mem. 2020 Oct;174:107282. PubMed Central PMCID: PMC7506508. 

Baratta AM, Kanyuch NR, Cole CA, Valafar H, Deslauriers J, Pocivavsek A. Acute sleep deprivation during pregnancy in rats: Rapid elevation of placental and fetal inflammation and kynurenic acid. Neurobiol Stress. 2020 May;12:100204. PubMed Central PMCID: PMC7109515. 

Baratta AM, Buck SA, Buchla AD, Fabian CB, Chen S, Mong JA, Pocivavsek A. Sex Differences in Hippocampal Memory and Kynurenic Acid Formation Following Acute Sleep Deprivation in Rats. Sci Rep. 2018 May 3;8(1):6963. doi: 10.1038/s41598-018-25288-w. PubMed Central PMCID: PMC5934413.

Pocivavsek A, Rowland LM. Basic Neuroscience Illuminates Causal Relationship Between Sleep and Memory: Translating to Schizophrenia. Schizophr Bull. 2018 Jan 13;44(1):7-14. doi: 10.1093/schbul/sbx151. PubMed Central PMCID: PMC5768044.

Pocivavsek A, Baratta AM, Mong JA, Viechweg SS. Acute Kynurenine Challenge Disrupts Sleep-Wake Architecture and Impairs Contextual Memory in Adult Rats. Sleep. 2017 Nov 1;40(11). doi: 10.1093/sleep/zsx141. PubMed Central PMCID: PMC5806560.

Erhardt S, Pocivavsek A, Repici M, Liu XC, Imbeault S, Maddison DC, Thomas MAR, Smalley JL, Larsson MK, Muchowski PJ, Giorgini F, Schwarcz R. Adaptive and Behavioral Changes in Kynurenine 3-Monooxygenase Knockout Mice: Relevance to Psychotic Disorders. Biol Psychiatry. 2017 Nov 15;82(10):756-765. doi: 10.1016/j.biopsych.2016.12.011. Epub 2016 Dec 16. PubMed Central PMCID: PMC5812460.

Pocivavsek A, Thomas MA, Elmer GI, Bruno JP, Schwarcz R. Continuous kynurenine administration during the prenatal period, but not during adolescence, causes learning and memory deficits in adult rats. Psychopharmacology (Berl). 2014 Jul;231(14):2799-809. doi: 10.1007/s00213-014-3452-2. Epub 2014 Mar 4. PubMed Central PMCID: PMC4074218.

Pocivavsek A, Wu HQ, Potter MC, Elmer GI, Pellicciari R, Schwarcz R. Fluctuations in endogenous kynurenic acid control hippocampal glutamate and memory. Neuropsychopharmacology. 2011 Oct;36(11):2357-67. doi: 10.1038/npp.2011.127. Epub 2011 Jul 27. PubMed Central PMCID: PMC3176574.

Find Dr. Pocivavsek on Pubmed.