Faculty Profile

Mark R. Zielinski, PhD


Assistant Professor of Psychiatry, Harvard Medical School
Research Health Scientist, Department of Psychiatry, VA Boston Healthcare System

Administrative Title(s)

Director of the Neuroimmunology and Sleep Laboratory

See publications


Email Mark_Zielinski@hms.harvard.edu

Society Memberships

Sleep Research Society
Society for Neuroscience

Research Unit(s)

Director of the Neuroimmunology and Sleep Laboratory, Laboratory of Neuroscience, Department of Psychiatry, VA Boston Healthcare System

Research Interests

My laboratory work focuses on neuroimmunology and sleep research. Individuals with sleep disorders, inflammatory-related pathologies, and psychiatric disorders can experience profound sleep disturbance impacting their health and quality of life. Inflammation can induce many of the same detriments that are found after sleep loss such as impaired cognition, performance, vigilance, and psychological state. Sleep is multifarious and is regulated globally, regionally, and locally by both cellular and molecular mechanisms. Numerous cellular and molecular mechanisms that regulate immunity also regulate sleep. In general, pro-inflammatory molecules enhance sleep, while anti-inflammatory molecules inhibit sleep induced by somnogenic conditions. Many pathogens and their components, such as influenza and the gram-negative bacteria cell wall component lipopolysaccharide enhance sleep, electroencephalogram delta power (0.5-4 Hz frequency range, an indicator of sleep need), and pro-inflammatory molecules in specific brain areas including the cortex. We found that both acute sleep loss and chronic sleep loss enhances pro-inflammatory molecules in the specific brain areas. Currently, the exact mechanisms that regulate the somnogenic properties of inflammatory molecules are unknown. We discovered exciting evidence indicating that the nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome protein complex, which activates a cascade of events leading to increased interleukin-1 beta (IL-1β), is critical to sleep induced by both sleep loss and lipopolysaccharide. Our laboratory uses molecular, immunological, and neuroscience methodologies to understand basic sleep mechanisms that will allow for future pharmaceutical treatments and strategies for veterans and individuals with dysregulated sleep.

Trainees

Gianne Souza, B.S., 2009-2011
Andrea Boucher, B.S., 2009-2011
Omar Bayomy, B.S., 2010-2011
Danielle Dunbrasky, B.S, 2010-2012
Madaleine Niznikiewicz, undergraduate, 2016-present
Alana M. Johnston, undergraduate, 2017-present

Mentor(s)


Research Funding

Veterans Affairs, PI: Mark R. Zielinski, PhD, Sleep loss and inflammation in the neurovascular unit

Selected Publications

Original Articles

Zielinski MR, Muenchow M, Wallig MA, Horn PL, Woods JA. Exercise delays allogeneic tumor growth and reduces intratumoral inflammation and vascularization. J Appl Physiol (1985). 2004 Jun; 96(6):2249-56, PMID: 15020578, PMCID: PMC3645346.

Kline CE, Durstine JL, Davis JM, Moore TA, Devlin TM, Zielinski MR, Youngstedt SD. Circadian variation in swim performance. J Appl Physiol (1985). 2007 Feb; 102(2):641-9.

Davis JM, Murphy EA, Carmichael MD, Zielinski MR, Groschwitz CM, Brown AS, Gangemi JD, Ghaffar A, Mayer EP. Curcumin effects on inflammation and performance recovery following eccentric exercise-induced muscle damage. Am J Physiol Regul Integr Comp Physiol. 2007 Jun; 292(6):R2168-73.

Zielinski MR, Kline CE, Kripke DF, Bogan RK, Youngstedt SD. No effect of 8-week time in bed restriction on glucose tolerance in older long sleepers. J Sleep Res. 2008 Dec; 17(4):412-9, PMID: 18691360, PMCID: PMC3244074.

Youngstedt SD, Kline CE, Zielinski MR, Kripke DF, Devlin TM, Bogan RK, Wilcox S, Hardin JW. Tolerance of chronic 90-minute time-in-bed restriction in older long sleepers. Sleep. 2009 Nov; 32(11):1467-79, PMID: 19928386, PMCID: PMC2768953.

Kline CE, Zielinski, MR, Devlin TM, Kripke DF, Bogan RK, Youngstedt SD. Self-reported long sleep in older adults is closely related to objective time in bed. Sleep and Biological Rhythms. 2010 Jan; 8(1):42-51, PMID: 25210491, PMCID: PMC4157821.

Krueger JM, Taishi P, De A, Davis CJ, Winters BD, Clinton J, Szentirmai E, Zielinski MR. ATP and the purine type 2 X7 receptor affect sleep. J Appl Physiol (1985). 2010 Nov; 109(5):1318-27, PMID: 20829501, PMCID: PMC2980381.

Youngstedt SD, Kline CE, Ginsberg JP, Zielinski MR, Hardin JW. Bright light treatment for high-anxious young adults: a randomized controlled pilot study. Depress Anxiety. 2011 Apr; 28(4):324-32, PMID: 21254315.

Taishi P, Davis CJ, Bayomy O, Zielinski MR, Liao F, Clinton JM, Smith DE, Krueger JM. Brain specific interleukin-1 receptor accessory protein in sleep regulation. J Appl Physiol (1985). 2012 Mar; 112(6):1015-22, PMID: 22174404, PMCID: PMC3311656.

Zielinski MR, Davis JM, Fadel JR, Youngstedt SD. Influence of chronic moderate sleep restriction and exercise on inflammation and carcinogenesis in mice. Brain Behav Immun. 2012 May; 26(4):672-9, PMID: 22433899, PMCID: PMC3645371.

Zielinski MR, Taishi P, Clinton JM, Krueger JM. 5'-Ectonucleotidase-knockout mice lack non-REM sleep responses to sleep deprivation. Eur J Neurosci. 2012 Jun; 35(11):1789-98, PMID: 22540145, PMCID: PMC3370120.

Zielinski MR, Gerashchenko L, Karpova SA, Gerashchenko D. A novel telemetric system to measure polysomnographic biopotentials in freely moving animals. J Neurosci Methods. 2013 Jun; 216(2):79-86, PMID: 23563323, PMCID: PMC3679249.

Zielinski MR, Davis JM, Fadel JR, Youngstedt SD. Influence of chronic moderate sleep restriction and exercise training on anxiety, spatial memory, and associated neurobiological measures in mice. Behav Brain Res. 2013 Aug; 250:74-80, PMID: 23644185, PMCID: PMC3801204.

Zielinski MR, Kim Y, Karpova SA, Winston S, McCarley RW, Strecker RE, Gerashchenko D. Sleep active cortical neurons expressing neuronal nitric oxide synthase are active after both acute sleep deprivation and chronic sleep restriction. Neuroscience. 2013 Sep; 247:35-42, PMID: 23685166, PMCID: PMC3801181.

Zielinski MR, Dunbrasky DL, Taishi P, Souza G, Krueger JM. Vagotomy attenuates brain cytokines and sleep induced by peripherally administered tumor necrosis factor-alpha and lipopolysaccharide in mice. Sleep. 2013 Aug; 36(8):1227-38, 1238A, PMID: 23904683, PMCID: PMC3700720.

Zielinski MR, Souza G, Taishi P, Bohnet SG, Krueger JM. Olfactory bulb and hypothalamic acute-phase responses to influenza virus: effects of immunization. Neuroimmunomodulation. 2013; 20(6):323-33, PMID: 239487, PMCID: PMC3874867.

Zielinski MR, Kim Y, Karpova SA, McCarley RW, Strecker RE, Gerashchenko D. Chronic sleep restriction elevates brain interleukin-1 beta and tumor necrosis factor-alpha and attenuates brain derived neurotrophic factor expression. Neurosci Lett. 2014 Sep; 580:27-31: PMID: 25093703, PMCID: PMC4162816.

Zielinski MR, Karpova SA, Xiaomei Y, Gerashchenko D. Substance P and the neurokinin-1 receptor regulates electroencephalogram non-rapid eye movement sleep slow-wave activity locally. Neuroscience 2015 Jan 22,284:260-72: PMID: 25301750, PMCID: PMC4268367.

Youngstedt SD, Kline CE, Elliott JA, Zielinski MR, Devlin TM, Moore A. Circadian phase-shifting effects of bright light, exercise, and bright light + exercise. J Circadian Rhythms 2016 Feb;14:2: PMID: 27103935, PMCID: PMC4834751.

Davis CJ, Zielinski MR, Dunbrasky D, Taishi P, Dinarello CA, Krueger JM. Interleukin 37 expression in mice alters sleep responses to inflammatory agents and influenza virus infection. Neurobiol Sleep Circadian Rhythms 2017. PMID: 28070566, PMCID: PMC5218600.

Zielinski MR, Gerashchenko D, Karpova SA, Konanki V, McCarley RW, Sutterwala FS, Strecker RE, Basheer R. The NLRP3 inflammasome modulates sleep and NREM sleep delta power induced by spontaneous wakefulness, sleep deprivation and lipopolysaccharide. Brain Behav Immun 2017 Jan 18. PMID: 28109896, PMCID: (PMID: 28109896, PMCID: PMC5373953).

Reviews, Books & Chapters

Youngstedt S, Kline C, Zielinski M, Devlin T, Lee A, Kripke D. Proceedings of the Interim Congress of the World Federation of Sleep Research and Sleep medicine Society: Clinical and Neurophysiological Aspects of Sleep. Kumar VM, Mallick HN, Eds. Moderate sleep restriction in older long sleepers. 2005; 161-166.

Youngstedt SD, Kripke DF, Kline CE, Zielinski MR, Bogan RK. Lack of impairment in glucose tolerance: support for further investigation of sleep restriction in older long sleepers. J Sleep Res. 2010 Mar; 19(1 Pt 1):116-7, PMID: 20470263.

Krueger JM, Clinton JM, Winters BD, Zielinski MR, Taishi P, Jewett KA, Davis CJ. Involvement of cytokines in slow wave sleep. Prog Brain Res. 2011; 193:39-47, PMID: 21854954, PMCID: PMC3645329.

Zielinski MR, Krueger JM. Sleep and innate immunity. Front Biosci (Schol Ed). 2011 Jan; 3:632-42, PMID: 21196401, PMCID: PMC3645929.

Clinton JM, Davis CJ, Zielinski MR, Jewett KA, Krueger JM. Biochemical regulation of sleep and sleep biomarkers. J Clin Sleep Med. 2011 Oct 15; 7(5 Suppl):S38-42, PMID: 22003330, PMCID: PMC3190410.

Davis CJ, Clinton JM, Jewett KA, Zielinski MR, Krueger JM. Delta wave power: an independent sleep phenotype or epiphenomenon? J Clin Sleep Med. 2011 Oct; 7(5 Suppl):S16-8, PMID: 22003323, PMCID: PMC3190419.

Zielinski MR, Krueger JM. Therapy in sleep medicine. Barkoukis TJ, Matheson JK, Ferber R, Doghramji K, eds. Sleep and Inflammation. 2012; 607-616.

Zielinski MR, Gerashchenko D. Diet and Exercise in Cognitive Function and Neurological Diseases, First Edition. Farooqui T, Farooqui AA, eds. Role of Sleep in Cognition, Immunity, and Disease and Its Interaction with Exercise. 2015; 225-239.

Zielinski MR, McKenna JT, McCarley RW. Functions and mechanisms of sleep. Aims Neuroscience. 2016 Apr; 3:67-104 (PMID: 28413828, PMCID: PMC5390528).

McKenna JT, Zielinski MR, McCarley RW. Sleep Disorders Medicine: Basic Science, Technical Considerations and Clinical Aspects, Fourth Edition. Chokroverty S, ed. Neurobiology of REM sleep, NREM Sleep Homeostasis, and Gamma Band Oscillations. 2017; 55-77.

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