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Vice Chair of Pharm & Phys
Interim Chair, Department of Pharmacology & Physiology
Professor of Pharmacology and Physiology
Professor of Anesthesiology and Critical Care Medicine (Secondary)
Office Phone: 202-994-3466
Department: Pharmacology and Physiology
- BSE, Pennsylvania, Univ of, 1981
- PhD, University of Washington, 1989
Recent (2020-2021) peer reviewed publications
- Sex Differences in the Hypothalamic Oxytocin Pathway to Locus Coeruleus and Augmented Attention with Chemogenetic Activation of Hypothalamic Oxytocin Neurons. Wang X, Escobar JB, Mendelowitz D. Int J Mol Sci. 2021 Aug 7;22(16):8510. doi: 10.3390/ijms22168510. PMID: 34445224 Free PMC article.
- The Effect of DREADD Activation of Leptin Receptor Positive Neurons in the Nucleus of the Solitary Tract on Sleep Disordered Breathing. Amorim MR, Dergacheva O, Fleury-Curado T, Pho H, Freire C, Mendelowitz D, Branco LGS, Polotsky VY. Int J Mol Sci. 2021 Jun 23;22(13):6742. doi: 10.3390/ijms22136742. PMID: 34201760 Free PMC article.
- Leptin receptor expression in the dorsomedial hypothalamus stimulates breathing during NREM sleep in db/db mice. Pho H, Berger S, Freire C, Kim LJ, Shin MK, Streeter SR, Hosamane N, Cabassa ME, Anokye-Danso F, Dergacheva O, Amorim MR, Fleury-Curado T, Jun JC, Schwartz AR, Ahima RS, Mendelowitz D, Polotsky VY. Sleep. 2021 Jun 11;44(6):zsab046. doi: 10.1093/sleep/zsab046. PMID: 33624805 Free PMC article.
- Optogenetic Control of Cardiac Autonomic Neurons in Transgenic Mice. Moreno A, Kowalik G, Mendelowitz D, Kay MW. Methods Mol Biol. 2021;2191:309-321. doi: 10.1007/978-1-0716-0830-2_18. PMID: 32865752 Free PMC article.
- Evidence of Superior and Inferior Sinoatrial Nodes in the Mammalian Heart. Brennan JA, Chen Q, Gams A, Dyavanapalli J, Mendelowitz D, Peng W, Efimov IR. JACC Clin Electrophysiol. 2020 Dec;6(14):1827-1840. doi: 10.1016/j.jacep.2020.09.012. Epub 2020 Nov 25. PMID: 33357580 Free PMC article.
- Cholinergic stimulation improves electrophysiological rate adaptation during pressure overload-induced heart failure in rats. Zasadny FM, Dyavanapalli J, Dowling NM, Mendelowitz D, Kay MW. Am J Physiol Heart Circ Physiol. 2020 Oct 2;319(6):H1358-68. doi: 10.1152/ajpheart.00293.2020. Online ahead of print. PMID: 33006920 Free PMC article.
- Intranasal oxytocin increases respiratory rate and reduces obstructive event duration and oxygen desaturation in obstructive sleep apnea patients: a randomized double blinded placebo controlled study. Jain V, Kimbro S, Kowalik G, Milojevic I, Maritza Dowling N, Hunley AL, Hauser K, Andrade DC, Del Rio R, Kay MW, Mendelowitz D. Sleep Med. 2020 Oct;74:242-247. doi: 10.1016/j.sleep.2020.05.034. Epub 2020 Jun 5. PMID: 32862007 Clinical Trial.
- Disrupted Coordination of Hypoglossal Motor Control in a Mouse Model of Pediatric Dysphagia in DiGeorge/22q11.2 Deletion Syndrome. Wang X, Popratiloff A, Motahari Z, LaMantia AS, Mendelowitz D. eNeuro. 2020 Oct 9;7(5):ENEURO.0520-19.2020. doi: 10.1523/ENEURO.0520-19.2020. Print 2020 Sep/Oct. PMID: 32855199 Free PMC article.
- Intranasal Leptin Prevents Opioid-induced Sleep-disordered Breathing in Obese Mice. Freire C, Pho H, Kim LJ, Wang X, Dyavanapalli J, Streeter SR, Fleury-Curado T, Sennes LU, Mendelowitz D, Polotsky VY. Am J Respir Cell Mol Biol. 2020 Oct;63(4):502-509. doi: 10.1165/rcmb.2020-0117OC. PMID: 32603263 Free PMC article.
- Activation of Oxytocin Neurons Improves Cardiac Function in a Pressure-Overload Model of Heart Failure. Dyavanapalli J, Rodriguez J, Rocha Dos Santos C, Escobar JB, Dwyer MK, Schloen J, Lee KM, Wolaver W, Wang X, Dergacheva O, Michelini LC, Schunke KJ, Spurney CF, Kay MW, Mendelowitz D. JACC Basic Transl Sci. 2020 May 25;5(5):484-497. doi: 10.1016/j.jacbts.2020.03.007. eCollection 2020 May. PMID: 32478209 Free PMC article.
- Chemogenetic activation of intracardiac cholinergic neurons improves cardiac function in pressure overload-induced heart failure. Dyavanapalli J, Hora AJ, Escobar JB, Schloen J, Dwyer MK, Rodriguez J, Spurney CF, Kay MW, Mendelowitz D. Am J Physiol Heart Circ Physiol. 2020 Jul 1;319(1):H3-H12. doi: 10.1152/ajpheart.00150.2020. Epub 2020 May 15. PMID: 32412778 Free PMC article.
- Persistent Feeding and Swallowing Deficits in a Mouse Model of 22q11.2 Deletion Syndrome. Welby L, Caudill H, Yitsege G, Hamad A, Bunyak F, Zohn IE, Maynard T, LaMantia AS, Mendelowitz D, Lever TE. Front Neurol. 2020 Jan 31;11:4. doi: 10.3389/fneur.2020.00004. eCollection 2020. PMID: 32082240 Free PMC article.
- GABA and glycine neurons from the ventral medullary region inhibit hypoglossal motoneurons. Dergacheva O, Fleury-Curado T, Polotsky VY, Kay M, Jain V, Mendelowitz D. Sleep. 2020 Jun 15;43(6):zsz301. doi: 10.1093/sleep/zsz301.
My research career is centered on the neurons in the brain and peripheral nervous system that control cardiorespiratory function with the goal of identifying new targets to reduce and/or prevent highly prevalent and devastating diseases, including obstructive sleep apnea (OSA), arrhythmias, hypertension, cardiac ischemia and heart failure. In 1996 I was the first investigator to study the voltage and ligand gated receptors, firing properties and function of cardiac vagal neurons that generate parasympathetic activity to the heart. My more recent work seeks to identify the mechanisms that maintain and/or generate dysfunction of parasympathetic activity and test if targeted manipulation of the receptors and neurotransmitters to these neurons can restore autonomic balance and improve treatment of cardiorespiratory diseases. Another major interest is the control of hypoglossal motor neurons in the brainstem that control tongue muscles and airway patency, particularly with risk factors for OSA. My lab tests these important clinically relevant hypotheses by quantifying changes both in-vivo and in-vitro. To test our hypotheses in conscious unrestrained animals we use approaches that include plethysmography, telemetry recordings of blood pressure, heart rate and heart rate variability while selectively altering the activity of specific neuronal targets using chemogenetic Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) that elicit long duration changes in the activity of targeted neurons. To test our hypotheses in-vitro we use optogenetic approaches, as promoter driven expression of channelrhodopsin (ChR2) permits selective photoexcitation of specific neurons and/or pathways while quantifying, using patch clamp electrophysiology, post-synaptic responses in targets such as cardiac vagal or hypoglossal neurons. Our most recent work provided the necessary foundation for clinical studies in which we show intranasal oxytocin provides benefits to patients with OSA. I have published over 130 peer-reviewed publications and have been continuously funded by NIH as a PI since 1993.
For more information, please visit the Mendelowitz Lab website
1 R01 HL146169-02, Dr. Matt Kay, PI, D. Mendelowitz co-I 12/1/18 – 11/31/2022 (NCE to 11/31/23)
Hypothalamic neuron activation to blunt myocardial remodeling during chronic sleep apnea.
Patients suffering from obstructive sleep apnea (OSA) have a 3-fold increase in cardiovascular mortality, yet very little is known regarding how OSA directly increases the risk for myocardial injury and disease. A goal of this project is to identify the specific impact of OSA on the cardiac function of rats exposed to chronic intermittent hypoxia (CIH), a model of OSA. Our studies will also test the innovative hypothesis that appropriately timed activation of a small population of hypothalamic paraventricular neurons will slow the development of, or reverse, the deleterious autonomic and cardiac function alterations that occur during OSA.
1R01HL147279-01 Mendelowitz (MPI) 04/10/2020-03/31/2024
Novel Mechanisms That Restore Cardiac Parasympathetic Activity Limits Arrhythmias And Cardiac Dysfunction After Myocardial Infarction
In this project we will test the hypothesis that the critical excitatory pathway from PVN oxytocin neurons to CVNs that helps maintain protective parasympathetic activity to the heart is blunted in animals following LAD ligation, and that this key neurotransmission can be restored with nasal oxytocin treatment and chronic and selective activation of PVN oxytocin neurons. We will also test whether treatment by nasal oxytocin and chronic and selective activation of PVN oxytocin neurons increases parasympathetic activity to the heart in-vivo, reduce the incidence of arrhythmias, improves autonomic balance and effort capacity in exercise stress tests and cardiac function, as well as quantify the electrical and mechanical function of ex-vivo perfused hearts to identify the mechanisms responsible for the cardiac benefits of nasal oxytocin and selective activation of PVN oxytocin neurons in LAD-ligated animals.
2R01 HL128970-05 Mendelowitz (subcontract- PI) 04/01/2020-03/31/2024
Treatment of Sleep Apnea by Targeting Leptin Signaling
Obstructive sleep apnea (OSA) is recurrent upper airway obstruction caused by a loss of upper airway muscle tone during sleep. There is no pharmacotherapy for OSA. Our efforts have focused on leptin, an adipocyte-produced hormone, which suppresses appetite, increases metabolic rate, and up-regulates control of breathing. In this subcontract to GW we will examine synaptic connections between LepRb+ neurons, originating from both the DMH and NTS, that project to and synapse upon hypoglossal motoneurons. We propose that both DMH and NTS LepRb+ neurons connect to hypoglossal motoneurons and that optogenetic stimulation of (A) DMH- and (B) NTS LepRb-channelrhodopsin (ChR2) expressing neurons and fibers activates hypoglossal motoneurons.
Centers and Institutes
GW Institute for Biomedical Sciences
Synaptic and intrinsic activation of GABAergic neurons in the cardiorespiratory brainstem network. Frank, JG, Mendelowitz, D. PLoS ONE, in press, 2012.
? adrenergic receptor modulation of neurotransmission to cardiac vagal neurons in the nucleus ambiguus. Bateman RJ, Boychuk CR, Philbin KE, Mendelowitz D. Neuroscience. 2012 Feb 24. [Epub ahead of print] PMID:22425752
Orexinergic modulation of GABAergic neurotransmission to cardiac vagal neurons in the brain stem nucleus ambiguus changes during development. Dergacheva O, Bateman R, Byrne P, Mendelowitz D. Neuroscience. 2012 May 3;209:12-20. Epub 2012 Feb 21. PMID:22390944
5HT1A receptors inhibit glutamate inputs to cardiac vagal neurons post-hypoxia/hypercapnia. Dergacheva O, Kamendi HW, Wang X, Mendelowitz D. Respir Physiol Neurobiol. 2011 Dec 15;179(2-3):254-8. PMID:21930251
?1-adrenergic receptors facilitate inhibitory neurotransmission to cardiac vagal neurons in the nucleus ambiguus. Boychuk CR, Bateman RJ, Philbin KE, Mendelowitz D. Neuroscience. 2011 Oct 13;193:154-61. PMID:21771639
Hypocretin-1 (orexin A) prevents the effects of hypoxia/hypercapnia and enhances the GABAergic pathway from the lateral paragigantocellular nucleus to cardiac vagal neurons in the nucleus ambiguus.Dergacheva O, Philbin K, Bateman R, Mendelowitz D. Neuroscience. 2011 Feb 23;175:18-23. PMID:21134420
GLP-1 receptor stimulation depresses heart rate variability and inhibits neurotransmission to cardiac vagal neurons. Griffioen KJ, Wan R, Okun E, Wang X, Lovett-Barr MR, Li Y, Mughal MR, Mendelowitz D, Mattson MP. Cardiovasc Res. 2011 Jan 1;89(1):72-8.
Industry Relationships and Collaborations
This faculty member (or a member of their immediate family) has reported a financial interest with the health care related companies listed below. These relations have been reported to the University and, when appropriate, management plans are in place to address potential conflicts.