Our research is focused on understanding how stress, obesity and aging affect neuroendocrine regulation of blood pressure with an aim to identify novel therapeutic targets for the treatment of hypertension and cardiovascular diseases.
The paraventricular nucleus of the hypothalamus (PVN) is a complex structure composed of several subgroups of neurons involved in maintaining homeostasis, regulating autonomic and endocrine responses to internal or external stressors and controlling food intake and energy expenditure. We are investigating these regulatory mechanisms within the PVN in order to better understand the ways stress, changes in diet, age and the combination of these factors lead to elevations in blood pressure.
Ongoing projects are aimed to reveal the roles of neurotrophins such as brain-derived neurotrophic factor (BDNF) within the PVN and their involvement in acute stress responses, adaptation to repeated stressors and regulation of food intake and energy balance. We use whole animal, in vivo techniques such as radiotelemetric measurement of blood pressure in conscious animals, sympathetic nerve activity recording, stereotactic brain injections of pharmacological agents and viral vectors as well as a wide range of molecular techniques.
Recent work in our laboratory demonstrated that BDNF and angiotensin II signaling interact within the PVN to elicit acute increases in blood pressure and sympathetic activity, and that inhibition of BDNF signaling in the PVN can diminish acute stress-induced hypertensive responses. Furthermore, we have shown that long-term upregulation of BDNF expression in the PVN leads to significant long-term increases in blood pressure in part by preventing brainstem noradrenergic neurons to exert their inhibitory role on PVN neurons that drive sympathetic activity.
People in the Lab
- Daniella Thorsdottir - Graduate Student
For a complete list of Dr. Benedek Erdos' publications, please visit PubMed.
- Tumer N, Sevtlov S, Whidden M, Kirichenko N, Prima V, Erdos B, Sherman A, Kobeissy F, Yezierski R, Scarpace PJ, Vierch C, Wang KW. Overpressure blast-wave induced brain injury elevates oxidative stress in the hypothalamus and catecholamine biosynthesis in the rat adrenal medulla. Neurosci Lett, 544:62-67, 2013 Jun 7. PMID: 23570732
- Daubert DL, McCowan M, Erdos B, Scheuer D. Nucleus of the Solitary Tract catecholamineric neurons modulate the cardiovascular response to physiological stress in rats. J Physiol. 590:4881-4895, 2012 Oct 1. PMID: 22753543
- Erdos B, Kirichenko N, Whidden M, Basgut B, Woods ME, Cudykier I, Tawil R, Scarpace PJ, Tumer N. Effect of age on hing fat diet-induced hypertension. Am J Physiol Heart Circ Physiol. 301: H164172, 2011 May 6. PMID: 21551274
- Whidden M, Kirichenko N, Halic Z, Erdos B, Foster TC, Tumer N. Lifelong caloric restriction prevents age-induced oxidative stress in the sympathoadreal system of Fischer 344 x Brown Norway rats. Biochem Biophys Res Commun, 408:454-458, 2011 April 19. PMID: 21527245
- Zhang Y, Rodrigues E, Gao YX, King M, Cheng KY, Erdos B, Tumer N, Carter C, Scarpace PJ. Pro-opionmelanocorin Gene Transfer to the NTS but not ARC Ameliorates Chronic Diet-Induced Obesity. Neuroscience, 169: 1662-1671, 2010 Sept 15. PMID: 20538045
- Erdos B, Cudykier I, Woods ME, Basgut B, Whidden M, Tawil R, Cardounel AJ, Tumer N. Hypertensive effects of central angiotensin II infusion and restraint stress are reduced with age. J Hypertens, 28:1298306, 2010 Jun 28. PMID: 20308921
- Erdos B, Broxson CS, Cudykier I, Basgut B, Whidden M, Landa T, Scarpace PJ, Tumer N. Effect of high fat diet feeding on hypothalamic redox signaling and central blood pressure regulation. Hypertens Res. 32-983-8, 2009 Aug 28. PMID: 19713964
- Manfredsson FP, Tumer N, Erdos B, Landa T, Broxson CS, Sullivan LF, Rising AC, Foust KD, Zhang Y, Muzyczka N, Gorbatyuk OS, Scarpace PJ, Mandel RJ. Nigrostriatal rAAV-mediated GDNF overexpression induces robust weight loss in a rat model of age-related obesity. Mol Ther, 17: 980-991, 2009 Mar 10. PMID: 19277011
- Erdos B, Erdem SR, Erdem A, Broxson CS, Tumer N. Effect of age on angiotensin II-mediated downregulation of adrenomedullary catecholamine biosynthetic enzymes. Exp Gerontol, 43(8): 806809, 2008 Aug. PMID: 18522866
- Tumer N, Erdos B, Matheny M, Cudykier I, Scarpace PJ. Leptin antagonist reverses hypertension due to leptin over-expression, but fails to normalize obesity-related hypertension. J Hypertens, 25(12): 2471-2478, 2007 Dec. PMID: 17984669
- Erdos B, Broxson CS, Landa T, Scarpace PJ, Leeuwenburgh C, Zhang Y, Tumer N. Effects of lifelong caloric restriction and voluntary exercise on age-related changes in levels of catecholamine biosynthetic enzymes and angiotensin II receptors in the rat adrenal medulla and hypothalamus. Experimental Generontology, 42(8): 745-752, 2007 Aug. PMID: 17540525
- Mersich T, Szelke E, Erdos B, Lacza Z, Komiati K, Sandor P. Somatosensory pain does not affect total cerebral blood volume. Neuroreport, 18: 649-652, 2007 May 7. PMID: 17426592
- Busija DW, Miller AW, Katakam P, and Erdos B. Adverse Effects of Reactive Oxygen Species on Vascular Reactivity in Insulin Resistance. Antioxi Redox Signal, 8: 1131-1140, 2006 Jul-Aug. PMID: 16910761
- Erdos B, Broxon CS, King MA, Scarpace PJ, Tumer N. Acute pressor effect of central angiotensin II is mediated by NAD(P)H-oxidase-dependent production of superoxide in the hypothalamic cardiovascular regulatory nuclei. J Hypertens. 24: 109-116, 2006 Jan. PMID: 16331108
- Erdos B, Snipes JA, Tulbert CD, Katakam P, Miller AW, Busija DW. Rosuvastatin improves cerebrovascular function in ZUker obese rats by inhibiting NAD(P)H-oxidase-dependent superoxide production. Am J Physiol Heart Circ Physiol 290: H1264-H1270, 2006 Mar. PMID: 16284235
- Krizbai IA, Lenzser G, Szatmari E, Farkas AE, Wilhelm I, Fekete Z, Erdos B, Bauer H, Bauer HC, Sandor P, Komjati K. Blood-brain barrier changes during compensated and decompensated hemorrhagic shock. Shock, 24: 428-433, 2005 Nov. PMID: 16247328
7/1/2011 - 6/30/2015
American Heart Association - Scientist Development Grant: “Hydrogen peroxide and age-related sympathetic nervous system dysregulation”
The central hypothesis of this grant is that reduced nerve growth factor production and catalase downregulation with age lead to elevated levels of hydrogen peroxide in the hypothalamus and brainstem resulting in a decline in catecholaminergic neuronal function and sympathetic nervous system dysregulation.