Stress, either of physical or psychological origin, has been implicated as a trigger for a number of devastating autoimmune and neuropsychiatric disorders, such as lupus erythematosus, depression, and schizophrenia. While we have a firm understanding of the physiology of the final common effectors involved in the stress response, i.e., corticotropin-releasing hormone and vasopressin, our knowledge of brain mechanisms activating the hypothalamic-pituitary-adrenal axis is more limited. Clearly, the glucocorticoids have powerful consequences associated with their hypersecretion during and after stress. However, the underlying neural mechanisms providing input to the neurons of the paraventricular nucleus are the substrates of neuropsychiatric illness. A more detailed understanding of the molecular and cellular relationships between neurotransmitters and neuromodulators in the regulation of hypothalamic-pituitary-adrenal axis secretions may provide keys to unlocking disorders, such as depression or schizophrenia or discoveries that may lead to new therapeutics for these disorders. Glutamate is the most abundant excitatory neurotransmitter in the neuroendocrine axis, and has been implicated in the etiology of schizophrenia, yet the physiological role of this excitatory amino acid transmitter is poorly understood in the regulation of the hypothalamic-pituitary-adrenal axis. One of the aims of the proposed studies is to characterize the molecular and cellular events elicited by excitatory amino acid receptor activation in the control of the secretions of the hypothalamic-pituitary-adrenal axis. Hypoglycemia, a well-characterized and readily controllable """"""""metabolic stress,"""""""" precipitates excitatory amino acid release in the brain. Consequently, another aim of these investigations is to employ molecular and neuroendocrinological techniques to explore the participation of excitatory amino acid receptor activation in the hypothalamic-pituitary-adrenal axis during hypoglycemia. These studies aim to reveal important new information about the regulation of stress hormone secretion by glutamate and may be significant in better understanding brain mechanisms in neuropsychiatric and other stress-related disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK052382-02
Application #
2905977
Study Section
Psychobiological, Biological, and Neurosciences Subcommittee (MHAI)
Program Officer
Smith, Philip F
Project Start
1998-06-20
Project End
2001-05-31
Budget Start
1999-06-01
Budget End
2000-05-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Psychiatry
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
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Lee, P R; Brady, D; Koenig, J I (2003) Thyroid hormone regulation of N-methyl-D-aspartic acid receptor subunit mRNA expression in adult brain. J Neuroendocrinol 15:87-92
Koenig, James I; Kirkpatrick, Brian; Lee, Paul (2002) Glucocorticoid hormones and early brain development in schizophrenia. Neuropsychopharmacology 27:309-18