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Transforming the understanding and treatment of mental illness through research
DIVISION OF INTRAMURAL RESEARCH PROGRAMS
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 Principal Investigators

Lee E. Eiden, Ph.D.
Lee Eiden Photo   Lee E. Eiden is the Chief of the Section on Molecular Neuroscience in the National Institute of Mental Health Intramural Research Program of the National Institutes of Health, Bethesda, Maryland. He received his B.A. in Chemistry from Northwestern University in Evanston Illinois, and Ph.D. in Pharmacology from The University of Kansas, and did postdoctoral work in the NIMH Intramural Research Program before joining the faculty in 1985. His work at the NIH has focused on stimulus-secretion-synthesis coupling, characterization of the vesicular and secretory proteins mediating chemically coded neurotransmission, including chromogranin A, VMAT1, VMAT2, and VAChT and signaling pathways underlying neuropeptide-mediated stress responses. More recently, the laboratory has been involved in microarray- and bioinformatics-aided gene discovery within neuropeptide-dependent stress-activated cellular signaling pathways in the central nervous system. Dr. Eiden is a past or current member of the editorial boards of The Journal of Biological Chemistry, The Journal of Neurochemistry, Peptides and Science Signaling.
Research Interests

The overall goal of the Section on Molecular Neuroscience is to identify the cellular signaling components that allow neuropeptide GPCRs to control stress-responsive gene transcription. Pharmacological and genetic evidence indicates that neuropeptide slow transmitters represent “the language of the stressed nervous system” (Hokfelt et al., Lancet Neurology, 2003). Neuropeptide transmitters are important intervention points in injury, pain, drug abuse and stress. ‘Fast’, or ionotropic, neurotransmitters regulate ion flux through membrane receptors to control instantaneous firing rates of receptive cells. ‘Slow’, or metabotropic, neurotransmitters act through G-protein coupled receptors (GPCRs) to alter intracellular cyclic AMP or calcium levels, controlling gene transcription that encodes synaptic experience over longer periods. We hypothesize that  the linkage between stress-related signaling and the gene transcription required for neuronal protection against traumatic effects of stress will ultimately be established by examining a specific example of stress-related GPCR signaling from first messenger to gene activation, and uncovering its biochemical, pharmacological and physiological consequences. The pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide slow transmitter that elevates post-synaptic cyclic AMP (through Gs) and calcium (through Gq and other mechanisms) after secretion from pre-synaptic neurons. We have previously demonstrated that PACAP-deficient mice show impaired adrenomedullary responses to hypoglycemia and neuroprotective responses to brain ischemia. We recently discovered that PACAP is capable of enhancing transcription of specific target genes in neuroendocrine cells through a cyclic AMP-dependent mechanism that does not require protein kinase A (PKA). The cellular protein components of this ‘non-canonical’ cAMP transcriptional activation pathway are not known, although its importance in mediating cellular plasticity in the synaptic response to stress in both brain and peripheral neuroendocrine networks is quickly becoming clear. Without the full delineation of molecular pathways involved in cAMP-mediated neuronal response to metabolic, ischemic and psychogenic stress, development of innovative pharmacological therapeutic strategies to treat stress-associated disorders will be severely limited. Consequently, we aim to identify the cAMP sensor through which genes responsive to combinatorial calcium and cAMP signaling are uniquely activated by slow transmitters such as PACAP in both central and peripheral PACAP-responsive neurons, and deploy this biochemical information in development of pharmacological approaches to the management of the chronic stress response.

Representative Selected Recent Publications:
  • Ait-Ali, D., Stroth, N., Sen, J.M. and Eiden, L.E.: PACAP-cytokine interactions govern adrenal neuropeptide biosynthesis after systemic administration of LPS. Neuropharmacol., 58(1):208-214, 2010. (view)
  • Stroth, N. and Eiden, L.E.: Stress hormone synthesis triggered by restraint in mouse hypothalamus and adrenal gland is dependent on PACAP signaling. Neuroscience,65(4): 1025-1030, 2010. (view)
  • Mustafa, T., Walsh, J., Grimaldi, M. and Eiden, L.E. PAC1hop receptor activation facilitates catecholamine secretion selectively through 2-APB-sensitive Ca2+ channels in PC12 cells. Cellular Signaling, 22:1420-1426, 2010. (view)
  • Ait-Ali, D., Samal, B., Mustafa, T. and Eiden, L.E. Neuropeptides, growth factors, and cytokines: A cohort of informational molecules whose expression is up-regulated by the stress-associated slow transmitter PACAP in chromaffin cells. Cell. Mol. Neurobiol., 30: 1441-1449, 2010. (view)
  • Depboylu, C., Weihe, E. and Eiden, L.E. COX1 and COX2 expression in non-neuronal cellular compartments of the rhesus macaque brain during lentiviral infection. Neurobiol. Disease, 42: 108-115, 2011. (view)
  • Liu, X., Xu, W., Russ, J., Eiden, L.E. and Eiden, M.V. The host range of gamaretroviruses and gammaretroviral vectors includes post-mitotic neural cells. PLoS One, 6: e18072, 2011. (view)

 


Address:
Molecular Neuroscience Section
Laboratory of Cellular and Molecular Regulation
Building 49
Room 5A-38
9000 Rockville Pike
Bethesda MD 20892
Phone: 301) 496-4110
Email Dr. Eiden
Fax: (301) 402-1748
Lab Web Site: http://intramural.nimh.nih.gov/lcmr/smn/
   
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This page was last updated September 13, 2012.


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