ACTIONS OF CYTOKINES ON BRAIN FUNCTION

  • Friedman, Wilma (PI)
  • FRIEDMAN, WILMA (PI)
  • FRIEDMAN, WILMA (PI)
  • FRIEDMAN, WILMA (PI)

Project Details

Description

DESCRIPTION: (Applicant's Abstract): Inflammatory cytokines are present
in the brain during development and consequent to a variety of
neurological insults ranging from local lesions to neurodegenerative
disease. The functions subserved by cytokines in the nervous system are
poorly understood, however these molecules may mediate the effects of
inflammatory responses on neural function, and provide a critical link
between the immune and nervous systems. Initial studies from our lab and
others have shown that interleukin-1 (Il-1), an important
immunomodulatory cytokine, regulates expression of nerve growth factor
(NGF), a neurotrophic factor critical for neuronal survival and function.
The overall objective of this proposal is to define mechanisms governing
the interaction between cytokines and neurotrophic factors in the brain.
To identify potential cytokine-responsive cellular populations,
expression of receptors for Il-1 and the related cytokine TNF will be
localized in the adult and neonatal brain using in situ hybridization.
To determine whether neurons and/or glial cells respond to cytokines,
hippocampal cultures will be grown as separate neuronal or glial cultures
and exposed to Il-1 and related inflammatory cytokines TNF and Il-6. NGF
mRNA, expressed by both hippocampal neurons and astrocytes in culture,
will be examined in the separate populations for responsiveness to
cytokines. In addition, other members of the neurotrophin gene family,
BDNF and NT-3, which are also expressed in the hippocampus, will be
examined for regulation by inflammatory cytokines. Mechanisms underlying
regulation of NGF by Il-1 will be characterized. The Il-1 signal
transduction pathway will be examined by assessing the involvement of
different second messenger systems, and by investigating the role of
transcription factors such as AP-1 and NFkappaB. Thus, we propose to
further define the mechanisms by which immunomodulatory cytokines
influence neuronal function.
StatusFinished
Effective start/end date2/1/931/31/98

Funding

  • National Institute of Neurological Disorders and Stroke

ASJC

  • Clinical Neurology
  • Neurology

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