Acute and chronic disease and immunotherapy--for viral diseases or cancer-- are frequently accompanied by neurological manifestations including anorexia. Our previous behavioral studies showed that interleukin-1beta (IL-1beta), depending on the concentration (pathophysiological or pharmacological), induces anorexia by suppressing meal size, meal duration and metal frequency. In this application we propose an integrative approach. To investigate the cellular and molecular mechanisms by which IL-1beta affects a pivotal hypothalamic feeding-associated site (the ventromedial hypothalamic nucleus on VMN to induce anorexia. Our previous neurophysiological studies observed that IL-1beta acts specifically on VMN glucose-sensitive neurons that are proposed to participate in the control of feeding; glucose insensitive neurons are no affected indicating specificity of action. However, the cellular mechanisms involved in the modulation of VMN activity by Il-1beta are unknown. The studies proposed will examine the cellular and molecular mechanisms associated with the responses to the application of IL-1beta. Because very little is known on the cellular and molecular actions of Il-1 any information obtained from the proposed studies will be important. The characterization of the mechanisms by which IL-1beta affects the CNS is essential to: (1) the understanding of cytokine-nervous system interactions that result in anorexia during disease or immunotherapy; and (2) the development of pharmacological manipulations that will lead to the minimization of neurotoxicity of immunotherapy

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH056082-03
Application #
2675526
Study Section
Special Emphasis Panel (ZMH1-BRB-T (M4))
Project Start
1996-09-30
Project End
1999-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Delaware
Department
Other Health Professions
Type
Schools of Arts and Sciences
DUNS #
059007500
City
Newark
State
DE
Country
United States
Zip Code
19716
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Plata-Salaman, C R; Peloso, E; Satinoff, E (1998) Interleukin-1beta-induced fever in young and old Long-Evans rats. Am J Physiol 275:R1633-8
Plata-Salaman, C R; Peloso, E; Satinoff, E (1998) Cytokine-induced fever in obese (fa/fa) and lean (Fa/Fa) Zucker rats. Am J Physiol 275:R1353-7