Accession Number : ADA329143

Title :   IL-1 Effects in Brain.

Descriptive Note : Final rept. 1 Jun 91-31 Dec 96,

Corporate Author : TUFTS UNIV BOSTON MA SCHOOL OF MEDICINE

Personal Author(s) : Miller, Lawrence G. ; Fahey, Jeanne M.

PDF Url : ADA329143

Report Date : 28 AUG 1997

Pagination or Media Count : 5

Abstract : This research explored the effect of cytokines and neurosteroids on the GABAergic and I glutamatergic neurotransmitter systems in the CNS. lnterleukin-1 (IL-1) augmented GABAA receptor function in behavioral, neurochemical and electrophysiological paradigms both in vivo and in vitro. These effects of IL-1 were inhibited by the IL-1 receptor antagonist suggesting an indirect effect of IL-1 at its own receptor in the modulation of the GABAA receptor. Subsequent experiments demonstrated a negative modulatory role of IL-1 on NMDA receptor-mediated intracellular calcium increases which was unique to both IL-1 and to the NMDA receptor. These results provided the first direct evidence of a functional interaction of IL-1 with the NMDA receptor and implies a beneficial role of this cytokine in neurodegenerative processes. Additional work in our laboratory confirmed that pregnenolone sulfate (PS) potentiated the NMDA receptor-mediated increases in calcium flux, most likely acting at a unique steroid recognition site on the NMDA receptor. Further studies demonstrated a neurotoxic effect of PS on these cortical neurons in vitro. This study also demonstrated a synergistic toxic effect of PS and NMDA/glycine, providing additional evidence of the possible involvement of PS in the excitotoxic damage.

Descriptors :   *BRAIN, *IN VITRO ANALYSIS, *RECOGNITION, *IN VIVO ANALYSIS, FUNCTIONS, CALCIUM, DAMAGE, MODELS, TOXICITY, FLUX(RATE), NERVE CELLS, NEUROCHEMISTRY, SULFATES, MODULATION, NEUROTRANSMITTERS, SENSE ORGANS, SYNERGISM, ELECTROPHYSIOLOGY, GLYCINE, NEUROTOXINS, STEROIDS.

Subject Categories : Anatomy and Physiology
      Toxicology

Distribution Statement : APPROVED FOR PUBLIC RELEASE