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Anatomy and Neurobiology
Ph.D., Northwestern University, 1983
Sympathetic ganglia use both small molecule classical neurotransmitters and neuropeptides as chemical messengers. The coexpression of bioactive peptides and neurotransmitters permits functional diversity in the nervous system; however, the regulatory signals that modulate neurotransmitter and neuropeptide expression and neuroplasticity are poorly understood. The principal neurons of the superior cervical ganglion (SCG) are a unique model system used extensively to examine the regulation of neuronal transmitter and peptide expression. Most SCG neurons are catecholaminergic, and these cells produce high levels of norepinephrine and neuropeptide Y (NPY), and lower levels of several other bioactive peptides. SCG neurons also exhibit neurochemical plasticity, and under specific conditions, change from a noradrenergic to dopaminergic, adrenergic, or cholinergic phenotype with coordinate changes in neuropeptide expression. Our research uses primary cultured SCG neurons, to examine regulatory factors, including presynaptic signals, hormones, growth factors, cytokines, and target tissue factors, that modulate SCG neurotransmitter and neuropeptide expression. The questions we are addressing include: (1) What external signals or factors regulate sympathetic neuron transmitter and peptide expression? (2) What intracellular signaling pathways mediate these regulatory events? (3) What cellular processes, such as transcription, biosynthesis, and secretion, are modulated to alter neurotransmitter and neuropeptide expression? (4) What mechanisms are involved in altered gene expression? (5) How do these factors modulate sympathetic neuron survival, differentiation, and signaling? Our studies use a combination of disciplines, including biochemistry, cell biology, and molecular biology to examine these questions.
Recently, our work has focused on the roles of presynaptic signal modulation of SCG functions. We demonstrated that preganglionic neurons in the spinal cord projecting to the SCG express the bioactive peptide pituitary adenylate cyclase-activating polypeptide (PACAP). Further investigations have identified and localized the specific isoforms of the PACAP-selective PAC1 receptor, a putative seven transmembrane G-protein-coupled receptor, expressed by sympathetic neurons. In SCG neurons, these receptors are coupled to the activation of multiple intracellular signaling pathways; we are currently characterizing the mechanisms by which PACAP activation of these second messenger pathways regulates sympathetic neuron development, function, neurophenotypic plasticity.
Ressler KJ, Mercer KB, Bradley B, Jovanovic T, Mahan A, Kerley K, Norrholm SD, Kilaru V, Smith AK, Myers AJ, Ramirez M, Engel A, Hammack SE, Toufexis D, Braas KM, Binder EB, May V. Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature. 2011;470(7335):492-7.
Pérez-Monter C, Martínez-Armenta M, Miquelajauregui A, Furlan-Magaril M, Varela-Echavarría A, Recillas-Targa F, May V, Charli JL, Pérez-Martínez L. The Krüppel-like factor 4 controls biosynthesis of thyrotropin-releasing hormone during hypothalamus development. Mol Cell Endocrinol. 2011;333(2):127-33.
Hammack SE, Roman CW, Lezak KR, Kocho-Shellenberg M, Grimmig B, Falls WA, Braas K, May V. Roles for pituitary adenylate cyclase-activating peptide (PACAP) expression and signaling in the bed nucleus of the stria terminalis (BNST) in mediating the behavioral consequences of chronic stress. J Mol Neurosci. 2010;42(3):327-40.
May V, Lutz E, MacKenzie C, Schutz KC, Dozark K, Braas KM. Pituitary adenylate cyclase-activating polypeptide (PACAP)/PAC1HOP1 receptor activation coordinates multiple neurotrophic signaling pathways: Akt activation through phosphatidylinositol 3-kinase gamma and vesicle endocytosis for neuronal survival. J Biol Chem. 2010;285(13):9749-61.
Hammack SE, Cheung J, Rhodes KM, Schutz KC, Falls WA, Braas KM, May V. Chronic stress increases pituitary adenylate cyclase-activating peptide (PACAP) and brain-derived neurotrophic factor (BDNF) mRNA expression in the bed nucleus of the stria terminalis (BNST): roles for PACAP in anxiety-like behavior. Psychoneuroendocrinology. 2009;34(6):833-43.
Girard BM, Wolf-Johnston A, Braas KM, Birder LA, May V, Vizzard MA. PACAP-mediated ATP release from rat urothelium and regulation of PACAP/VIP and receptor mRNA in micturition pathways after cyclophosphamide (CYP)-induced cystitis. J Mol Neurosci. 2008;36(1-3):310-20.
Studeny S, Cheppudira BP, Meyers S, Balestreire EM, Apodaca G, Birder LA, Braas KM, Waschek JA, May V, Vizzard MA. Urinary bladder function and somatic sensitivity in vasoactive intestinal polypeptide (VIP)-/- mice. J Mol Neurosci. 2008;36(1-3):175-87.
Girard BM, Malley SE, Braas KM, Waschek JA, May V, Vizzard MA. Exaggerated expression of inflammatory mediators in vasoactive intestinal polypeptide knockout (VIP-/-) mice with cyclophosphamide (CYP)-induced cystitis. J Mol Neurosci. 2008;36(1-3):188-99.
Jensen DG, Studeny S, May V, Waschek J, Vizzard MA. Expression of phosphorylated cAMP response element binding protein (p-CREB) in bladder afferent pathways in VIP-/- mice with cyclophosphamide (CYP)-induced cystitis. J Mol Neurosci. 2008;36(1-3):299-309.
Braas KM, Schutz KC, Bond JP, Vizzard MA, Girard BM, May V. Microarray analyses of pituitary adenylate cyclase activating polypeptide (PACAP)-regulated gene targets in sympathetic neurons. Peptides. 2007;28(9):1856-70.
Pavelock KA, Girard BM, Schutz KC, Braas KM, May V. Bone morphogenetic protein down-regulation of neuronal pituitary adenylate cyclase-activating polypeptide and reciprocal effects on vasoactive intestinal peptide expression. J Neurochem. 2007;100(3):603-16.
Girard BA, Lelievre V, Braas KM, Razinia T, Vizzard MA, Ioffe Y, El Meskini R, Ronnett GV, Waschek JA, May V. Noncompensation in peptide/receptor gene expression and distinct behavioral phenotypes in VIP- and PACAP-deficient mice. J Neurochem. 2006;99(2):499-513.
Braas KM, May V, Zvara P, Nausch B, Kliment J, Dunleavy JD, Nelson MT, Vizzard MA. Role for pituitary adenylate cyclase activating polypeptide in cystitis-induced plasticity of micturition reflexes. Am J Physiol Regul Integr Comp Physiol. 2006;290(4):R951-62.
Girard BM, May V, Bora SH, Fina F, Braas KM. Regulation of neurotrophic peptide expression in sympathetic neurons: quantitative analysis using radioimmunoassay and real-time quantitative polymerase chain reaction. Regul Pept. 2002 Nov 15;109(1-3):89-101.
May V, Schiller MR, Eipper BA, Mains RE. Kalirin Dbl-homology guanine nucleotide exchange factor 1 domain initiates new axon outgrowths via RhoG-mediated mechanisms. J Neurosci. 2002 Aug 15;22(16):6980-90.
Hansel, D. E., V. May, B. A. Eipper, G. V. Ronnett (2001). Pituitary adenylyl cyclase-activating peptides and alpha-amidation in olfactory neurogenesis and neuronal survival in vitro. J. Neurosci. 21:4625-36.
Beaudet, M. M., R. L. Parsons, K. M. Braas, and V. May (2000). Mechanisms mediating pituitary adenylate cyclase-activating polypeptide depolarization of rat sympathetic neurons. J. Neurosci. 20:7353-61.
Braas, K. M. and V. May (1999). Pituitary adenylate cyclase-activating polypeptides directly stimulate sympathetic neuron neuropeptide Y release through PAC1 receptor isoform activation of specific intracellular signaling pathways. J. Biol. Chem. 274:27702-27710.
Beaudet, M. M., K. M. Braas, and V. May (1998). Pituitary adenylate cyclase-activating polypeptide (PACAP) expression in sympathetic preganglionic projection neurons to the superior cervical ganglion. J. Neurobiol. 36:325-36.
May, V. and K. M. Braas (1995). Pituitary adenylate cyclase activating polypeptide (PACAP) regulation of superior cervical ganglion neuropeptide Y and catecholamine expression. J. Neurochem. 65:978-987.
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Last modified July 19 2012 12:28 PM