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| Miles Herkenham, Ph.D., Senior Investigator |
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Dr. Herkenham received a B.A. degree from Amherst College in 1970 and his Ph.D. in Physiological Psychology from Northeastern University in 1975. He did postdoctoral training with Dr. W.J.H. Nauta at M.I.T., where he began a long career in neuroanatomical localization studies. Dr. Herkenham joined the NIMH in 1977. He has published in the areas of neural connectivity, opioid and cannabinoid receptor localization, therapeutic actions of antidepressant drugs, and more recently, immune signal molecule induction and function in the brain. As Chief of the Section on Functional Neuroanatomy and Acting Chief of the Laboratory of Cellular and Molecular Regulation, Dr. Herkenham and his group explore the molecular, cellular, and intercellular bases for immune signaling in the brain in several animal models of inflammation, emotionality, and disease.
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Staff:
Research Interests:
Our group uses the tools of modern neuroanatomy to investigate nervous system regulatory events that occur in animals when they respond and adapt to immune challenges, drug administration, emotional challenges, or stress. Responsive brain structures and cell types are identified by in situ hybridization histochemistry, immunohistochemistry, and molecular tools. The group is currently studying the induction of immune signal molecules such as cytokines and other inflammatory triggers in the brain in several in vivo paradigms. Recent work focuses on the role of NF-kappaB signaling the brain, particularly within emotional circuitry and in response to physiological and pathological challenges. Whereas the role of this transcription factor in immune cells (and glia) is fairly well known, its role in neurons is largely unknown. We are currently characterizing genes regulated by NF-kappaB in neurons using various histochemical and biochemical approaches in mice and in cultured primary neurons. We use DNA microarray; knockout, transgenic, and reporter mice; bone marrow stem cells in chimera models; and viral-based delivery of DNA constructs to limbic system targets. Our behavioral and biochemical studies of NFKB1 knockout mice with altered transcription factor signaling are important because these mice display reduced anxiety and heightened startle. These and other distinctive behavioral phenotypes guide the cellular work aimed at understanding the molecular and biochemical bases for the altered emotionality.
Additonal information about the group can be found at the lab website, at http://intramural.nimh.nih.gov/lcmr/sfn/
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Selected Recent Publications:
Bryceson Y, Foster J A, Kuppusamy SP, Herkenham M, Long EO (2005) Expression of a killer cell receptor gene in plastic regions of the central nervous system, J. Neuroimmunology 161, 177-182.
Full Text/Abstract
Chakravarty S, Herkenham M (2005) Toll-like receptor 4 on non-hematopoietic cells sustains CNS inflammation during endotoxemia, independent of systemic cytokines, J. Neuroscience 25, 1788-1796.
Kassed CA, Herkenham M (2004) NF-kappaB p50-deficient mice show reduced anxiety-like behaviors in tests of exploratory drive and anxiety, Behav. Brain Res. 154, 577-584.
Full Text/Abstract
Foster JA, Puchowicz MJ, McIntyre DC, Herkenham M (2004) Activin mRNA induced during amygdala kindling shows a spatiotemporal progression that tracks the spread of seizures, J. Comp. Neurol 476, 91-102.
Full Text/Abstract
Proescholdt MG, Chakravarty S, Foster JA, Foti SB, Briley EM, Herkenham M (2002) Intracerebroventricular but not intravenous interleukin-1b induces widespread vascular-mediated leukocyte infiltration and immune signal mRNA expression followed by brain-wide glial activation, Neuroscience 112, 731�749.
Proescholdt MG, Quigley L, Martin R, Herkenham M (2002) Immunization with a cannabinoid receptor type 1 peptide results in experimental allergic meningo-cerebellitis in the Lewis rat: A model for cell-mediated autoimmune neuropathology, J. Neuroscience Research 70, 150-160.
Butterweck V, Winterhoff H, Herkenham M (2001) St. John�s wort, hypericin, and imipramine: a comparative analysis of mRNA levels in brain areas involved in HPA axis control following short-term and long-term administration in normal and stressed rats, Mol. Psychiatry 6, 547-564.
Full Text/Abstract
All Selected Publications
Contact Information:
Dr. Miles Herkenham
Laboratory of Cellular and Molecular Regulation, NIMH
Porter Neuroscience Research Center
Building 35, Room 1C-913
35 Convent Drive, MSC 3724
Bethesda, MD 20892-3724
Telephone: (301) 496-8287 (office),
(301) 402-2200 (fax)
Email: herkenh@mail.nih.gov
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