Faculty Profile

Dmitry Gerashchenko, MD, PhD


Assistant Professor of Psychiatry, Harvard Medical School

See publications


Address

1400 VFW Parkway
Bldg. 3, Room 2A-107
West Roxbury, MA 02132
USA

Inter-office Mail Address

WX 151

Email dmitry_gerashchenko@hms.harvard.edu

Research Unit(s)

Laboratory of Neuroscience, Department of Psychiatry, VA Boston Healthcare System

Research Interests

The presence of large-amplitude, slow waves in the electroencephalogram (EEG) is a primary characteristic that distinguishes cerebral activity during sleep from that which occurs during wakefulness. We have identified a population of cells in the cortex that is activated during sleep and in which Fos expression parallels changes in the intensity of slow-wave activity in the EEG. These cortical neurons are a subset of GABAergic interneurons that express neuronal nitric oxide synthase (nNOS). Because these neurons are innvervated by neurotransmitter systems previously implicated in sleep/wake control, cortical nNOS neurons may be part of the neurobiological substrate that underlies homeostatic sleep regulation. Experimental studies also suggest the importance of these neurons in the regulation of memory. We use modern methods of neuroscience and novel genetic animal models (such as cell-specific knockout of nNOS in the cerebral cortex) to study the role of these neurons in sleep and memory.

Trainees

Maruyama Megumi, postgraduate, 2000
Deirdre Burns, undergraduate, 2007-2008
Rachael Lazar, undergraduate, 2006-2007
Ravi Pasumarthi, PhD, 2007-2009
Robert Boder, undergraduate, 2010
Alexander J. Davenport, undergraduate, 2010
Suraiya Begum, Research Fellow, 2011-2012
Mark Zielinski, PhD, 2012-2015
Svetlana Karpova, MD, 2012-2015

Mentor(s)

Priyattam J Shiromani, PhD

Research Funding

NIH/NINDS, PI: Dmitry Gerashchenko, MD, PhD, Title: Role of nNOS cortical neurons in slow wave activity production and cognition

NIH/Mobile Sleep Technologies, PI: Daniel Gartenberg, PhD, Title: Non-pharmacological improvement of sleep structure in older people

Selected Publications


Original Articles

Gerashchenko D, Pasumarthi RK, Kilduff TS. Plasticity-Related Gene Expression During Eszopiclone-Induced Sleep. Sleep. 2017 Jul 1;40(7). [PMID: 28605546]

Zielinski MR, Gerashchenko D. Sleep-inducing effect of substance P-cholera toxin A subunit in mice. Neuroscience letters. 2017; 659:44-47. [PMID: 28866052]

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, behavior, and immunity. 2017; 62:137-150. [PMID: 28109896]

Zielinski MR, Karpova SA, Yang X, Gerashchenko D. Substance P and the neurokinin-1 receptor regulate electroencephalogram non-rapid eye movement sleep slow-wave activity locally. Neuroscience. 2015; 284:260-72. [PMID: 25301750]

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. Neuroscience letters. 2014; 580:27-31. [PMID: 25093703]

Morairty SR, Dittrich L, Pasumarthi RK, Valladao D, Heiss JE, Gerashchenko D, Kilduff TS. A role for cortical nNOS/NK1 neurons in coupling homeostatic sleep drive to EEG slow wave activity. Proceedings of the National Academy of Sciences of the United States of America. 2013; 110(50):20272-7. [PMID: 24191004]

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; 247:35-42. [PMID: 23685166]

Zielinski MR, Gerashchenko L, Karpova SA, Gerashchenko D. A novel telemetric system to measure polysomnographic biopotentials in freely moving animals. Journal of neuroscience methods. 2013; 216(2):79-86. [PMID: 23563323]

Liu M, Blanco-Centurion C, Konadhode R, Begum S, Pelluru D, Gerashchenko D, Sakurai T, Yanagisawa M, van den Pol AN, Shiromani PJ. Orexin gene transfer into zona incerta neurons suppresses muscle paralysis in narcoleptic mice. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2011; 31(16):6028-40. [PMID: 21508228]

Gerashchenko D, Horvath TL, Xie XS. Direct inhibition of hypocretin/orexin neurons in the lateral hypothalamus by nociceptin/orphanin FQ blocks stress-induced analgesia in rats. Neuropharmacology. 2011; 60(4):543-9. [PMID: 21195099]

Wisor JP, Gerashchenko D, Kilduff TS. Sleep-active neuronal nitric oxide synthase-positive cells of the cerebral cortex: a local regulator of sleep? Current topics in medicinal chemistry. 2011; 11(19):2483-9. [PMID: 21906016]

Gerashchenko D, Wisor JP, Kilduff TS. Sleep-active cells in the cerebral cortex and their role in slow-wave activity. Sleep and biological rhythms. 2011; 9(s1):71-77. [PMID: 21625335]

Kilduff TS, Cauli B, Gerashchenko D. Activation of cortical interneurons during sleep: an anatomical link to homeostatic sleep regulation? Trends in neurosciences. 2011; 34(1):10-9. [PMID: 21030095]

Pasumarthi RK, Gerashchenko D, Kilduff TS. Further characterization of sleep-active neuronal nitric oxide synthase neurons in the mouse brain. Neuroscience. 2010; 169(1):149-57. [PMID: 20438808]

Thompson CL, Wisor JP, Lee CK, Pathak SD, Gerashchenko D, Smith KA, Fischer SR, Kuan CL, Sunkin SM, Ng LL, Lau C, Hawrylycz M, Jones AR, Kilduff TS, Lein ES. Molecular and anatomical signatures of sleep deprivation in the mouse brain. Frontiers in neuroscience. 2010; 4:165. [PMID: 21088695]

Hara J, Gerashchenko D, Wisor JP, Sakurai T, Xie X, Kilduff TS. Thyrotropin-releasing hormone increases behavioral arousal through modulation of hypocretin/orexin neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2009; 29(12):3705-14. [PMID: 19321767]

Gerashchenko D, Wisor JP, Burns D, Reh RK, Shiromani PJ, Sakurai T, de la Iglesia HO, Kilduff TS. Identification of a population of sleep-active cerebral cortex neurons. Proceedings of the National Academy of Sciences of the United States of  America. 2008; 105(29):10227-32. [PMID: 18645184]

Wisor JP, Pasumarthi RK, Gerashchenko D, Thompson CL, Pathak S, Sancar A, Franken P, Lein ES, Kilduff TS. Sleep deprivation effects on circadian clock gene expression in the cerebral cortex parallel electroencephalographic differences among mouse strains. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2008; 28(28):7193-201. [PMID: 18614689]

Terao A, Huang ZL, Wisor JP, Mochizuki T, Gerashchenko D, Urade Y, Kilduff TS. Gene expression in the rat brain during prostaglandin D2 and adenosinergically-induced sleep. Journal of neurochemistry. 2008; 105(4):1480-98. [PMID: 18331290]

Blanco-Centurion C, Gerashchenko D, Shiromani PJ. Effects of saporin-induced lesions of three arousal populations on daily levels of sleep and wake. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2007; 27(51):14041-8. [PMID: 18094243]

Blanco-Centurion C, Xu M, Murillo-Rodriguez E, Gerashchenko D, Shiromani AM, Salin-Pascual RJ, Hof PR, Shiromani PJ. Adenosine and sleep homeostasis in the Basal forebrain. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2006; 26(31):8092-100. [PMID: 16885223]

Gerashchenko D, Blanco-Centurion CA, Miller JD, Shiromani PJ. Insomnia following  hypocretin2-saporin lesions of the substantia nigra. Neuroscience. 2006; 137(1):29-36. [PMID: 16289583]

Gerashchenko D, Chou TC, Blanco-Centurion CA, Saper CB, Shiromani PJ. Effects of  lesions of the histaminergic tuberomammillary nucleus on spontaneous sleep in rats. Sleep. 2004; 27(7):1275-81. [PMID: 15586780]

Gerashchenko D, Shiromani PJ. Effects of inflammation produced by chronic lipopolysaccharide administration on the survival of hypocretin neurons and sleep. Brain research. 2004; 1019(1-2):162-9. [PMID: 15306250]

Desarnaud F, Murillo-Rodriguez E, Lin L, Xu M, Gerashchenko D, Shiromani SN, Nishino S, Mignot E, Shiromani PJ. The diurnal rhythm of hypocretin in young and  old F344 rats. Sleep. 2004; 27(5):851-6. [PMID: 15453542]

Shiromani PJ, Xu M, Winston EM, Shiromani SN, Gerashchenko D, Weaver DR. Sleep rhythmicity and homeostasis in mice with targeted disruption of mPeriod genes. American journal of physiology. Regulatory, integrative and comparative physiology. 2004; 287(1):R47-57. [PMID: 15031135]

Blanco-Centurion C, Gerashchenko D, Salin-Pascual RJ, Shiromani PJ. Effects of hypocretin2-saporin and antidopamine-beta-hydroxylase-saporin neurotoxic lesions  of the dorsolateral pons on sleep and muscle tone. The European journal of neuroscience. 2004; 19(10):2741-52. [PMID: 15147308]

Gerashchenko D, Shiromani PJ. Different neuronal phenotypes in the lateral hypothalamus and their role in sleep and wakefulness. Molecular neurobiology. 2004; 29(1):41-59. [PMID: 15034222]

Murillo-Rodriguez E, Blanco-Centurion C, Gerashchenko D, Salin-Pascual RJ, Shiromani PJ. The diurnal rhythm of adenosine levels in the basal forebrain of young and old rats. Neuroscience. 2004; 123(2):361-70. [PMID: 14698744]

Gerashchenko D, Murillo-Rodriguez E, Lin L, Xu M, Hallett L, Nishino S, Mignot E, Shiromani PJ. Relationship between CSF hypocretin levels and hypocretin neuronal  loss. Experimental neurology. 2003; 184(2):1010-6. [PMID: 14769395]

Gerashchenko D, Blanco-Centurion C, Greco MA, Shiromani PJ. Effects of lateral hypothalamic lesion with the neurotoxin hypocretin-2-saporin on sleep in Long-Evans rats. Neuroscience. 2003; 116(1):223-35. [PMID: 12535955]

Salin-Pascual R, Gerashchenko D, Greco M, Blanco-Centurion C, Shiromani PJ. Hypothalamic regulation of sleep. Neuropsychopharmacology : official publication  of the American College of Neuropsychopharmacology. 2001; 25(5 Suppl):S21-7. [PMID: 11682269]

Gerashchenko D, Kohls MD, Greco M, Waleh NS, Salin-Pascual R, Kilduff TS, Lappi DA, Shiromani PJ. Hypocretin-2-saporin lesions of the lateral hypothalamus produce narcoleptic-like sleep behavior in the rat. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2001; 21(18):7273-83. [PMID: 11549737]

Gerashchenko D, Salin-Pascual R, Shiromani PJ. Effects of hypocretin-saporin injections into the medial septum on sleep and hippocampal theta. Brain research. 2001; 913(1):106-15. [PMID: 11532254]

Scammell TE, Gerashchenko DY, Mochizuki T, McCarthy MT, Estabrooke IV, Sears CA,  Saper CB, Urade Y, Hayaishi O. An adenosine A2a agonist increases sleep and induces Fos in ventrolateral preoptic neurons. Neuroscience. 2001; 107(4):653-63. [PMID: 11720788]

Beuckmann CT, Lazarus M, Gerashchenko D, Mizoguchi A, Nomura S, Mohri I, Uesugi A, Kaneko T, Mizuno N, Hayaishi O, Urade Y. Cellular localization of lipocalin-type prostaglandin D synthase (beta-trace) in the central nervous system of the adult rat. The Journal of comparative neurology. 2000; 428(1):62-78. [PMID: 11058225]

Gerashchenko D, Okano Y, Urade Y, Inoué S, Hayaishi O. Strong rebound of wakefulness follows prostaglandin D2- or adenosine A2a receptor agonist-induced sleep. Journal of sleep research. 2000; 9(1):81-7. [PMID: 10733693]

Gerashchenko D, Beuckmann CT, Kanaoka Y, Eguchi N, Gordon WC, Urade Y, Bazan NG,  Hayaishi O. Dominant expression of rat prostanoid DP receptor mRNA in leptomeninges, inner segments of photoreceptor cells, iris epithelium, and ciliary processes. Journal of neurochemistry. 1998; 71(3):937-45. [PMID: 9721719]

Scammell T, Gerashchenko D, Urade Y, Onoe H, Saper C, Hayaishi O. Activation of ventrolateral preoptic neurons by the somnogen prostaglandin D2. Proceedings of the National Academy of Sciences of the United States of America. 1998; 95(13):7754-9. [PMID: 9636223, PMCID: PMC22747]

Gerashchenko DY, Beuckmann CT, Marcheselli VL, Gordon WC, Kanaoka Y, Eguchi N, Urade Y, Hayaishi O, Bazan NG. Localization of lipocalin-type prostaglandin D synthase (beta-trace) in iris, ciliary body, and eye fluids. Investigative ophthalmology & visual science. 1998; 39(1):198-203. [PMID: 9430563]

Beuckmann CT, Gordon WC, Kanaoka Y, Eguchi N, Marcheselli VL, Gerashchenko DY, Urade Y, Hayaishi O, Bazan NG. Lipocalin-type prostaglandin D synthase (beta-trace) is located in pigment epithelial cells of rat retina and accumulates within interphotoreceptor matrix. The Journal of neuroscience : the official journal of the Society for Neuroscience. 1996; 16(19):6119-24. [PMID: 8815894]

Gerashchenko D, Matsumura H. Continuous recordings of brain regional circulation  during sleep/wake state transitions in rats. The American journal of physiology.  1996; 270(4 Pt 2):R855-63. [PMID: 8967416]

Gerashchenko D, Gorenshtein B, Pyzhik T, Ostrovsky Yu. Influence of pyruvate, threonine and phosphoethanolamine on activities of some acetaldehyde-producing enzymes. Alcohol and alcoholism (Oxford, Oxfordshire). 1993; 28(4):437-43. [PMID: 8397525]

Gerashchenko DIu, Gorenshteĭn BI, Pyzhik TN, Ostrovskiĭ IuM. [Effect of pyrazole  on the activity of acetaldehyde-producing enzymes in the liver]. Ukrainskii biokhimicheskii zhurnal (1978). 1993; 65(4):99-102. [PMID: 8284830]

Possible mechanisms of acetaldehyde reduction in mitochondria in liver Gerashchenko D, Karput S, Ostrovsky Y. Vesti Akademii Nauk Belarusi. 1993; (2):73-76.

Ostrovskiĭ IuM, Nemeria NS, Zabrodskaia SV, Gerashchenko DIu. [Coenzyme-binding sites of the brain pyruvate dehydrogenase complex]. Ukrainskii biokhimicheskii zhurnal (1978). 1992; 64(3):46-51. [PMID: 1440965]

Metabolism of threonine in liver: Threonine aldolase and its properties Gorenshtein B, Gerashchenko D, Osrtovsky Y. Doklady Akademii Nauk Belarusi. 1991; 35:1127-1129.

Gas-chromatographic analysis for determination of O-phosphorylethanolamine ammonialyase activity in liver of animals Pyzhic T, Gerashchenko D, Ostrovsky Y. Vesti Academii Nauk Belarusi. 1991; (6):45-47.

Reviews, Chapters, and Books

Diet and Exercise in Cognitive Function and Neurological DiseasesZielinski MR, Gerashchenko D. Farooqui T, Farooqui AA, editors. Hoboken, NJ: John Wiley & Sons, Inc; 2015. Chapter 20, Role of Sleep in Cognition, Immunity, and Disease and Its Interaction with Exercise; p.225-239.

Proceedings of the Interim Congress of the World Federation of Sleep Research and Sleep Medicine Societies Desarnaud F, Xu M, Murillo-Rodriguez E, Rector T, Gerashchenko D, Shiromani PJ. Kumar VM, Mallick HN, editors. Bologna, Italy: Medimond Press; 2005. Gene expression profiling in the posterior hypothalamus of young and old F344 rats: Implications for sleep changes with aging; p.191-205.

Sleep Neurobiology and Circuitry Shiromani PJ, Gerashchenko D, Blanco-Centurion C, Murillio-Rodrigues E, Desarnaud F. Kushida C, LeEnfant C, editors. NY: Marcel Dekker; 2004. Chapter 19, Criteria for classifying genes as “wake” or “sleep” genes; p.399-413.

Molecular Neurosurgery With Targeted Toxins Blanco-Centurion C, Gerashchenko D, Murillio-Rodrigues E, Desarnaud F, Shiromani  PJ. Wiley R, Lappi DA, editors. Totowa, NJ: Humana Press Inc.; 2004. Chapter 11, The use of saporin conjugates to dissect neurons responsible for sleep and wakefulness; p.249-263.

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