       Document 0203
 DOCN  M9610203
 TI    Synaptic activation of NF-kappa B by glutamate in cerebellar granule
       neurons in vitro.
 DT    9601
 AU    Guerrini L; Blasi F; Denis-Donini S; Department of Genetics and
       Microbial Biology, University of; Milan, Italy.
 SO    Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9077-81. Unique Identifier
       : AIDSLINE MED/96016112
 AB    Neuronal proliferation, migration, and differentiation are regulated by
       the sequential expression of particular genes at specific stages of
       development. Such processes rely on differential gene expression
       modulated through second-messenger systems. Early postnatal mouse
       cerebellar granule cells migrate into the internal granular layer and
       acquire differentiated properties. The neurotransmitter glutamate has
       been shown to play an important role in this developmental process. We
       show here by immunohistochemistry that the RelA subunit of the
       transcription factor NF-kappa B is present in several areas of the mouse
       brain. Moreover, immunofluorescence microscopy and electrophoretic
       mobility-shift assay demonstrate that in cerebellar granule cell
       cultures derived from 3- to 7-day-old mice, glutamate specifically
       activates the transcription factor NF-kappa B, as shown by binding of
       nuclear extract proteins to a synthetic oligonucleotide reproducing the
       kappa B site of human immunodeficiency virus. The use of different
       antagonists of the glutamate recpetors indicates that the effect of
       glutamate occurs mainly via N-methyl-D-aspartate (NMDA)-receptor
       activation, possibly as a result of an increase in intracellular Ca2+.
       The synaptic specificity of the effect is strongly suggested by the
       observation that glutamate failed to activate NF-kappa B in astrocytes,
       while cytokines, such as interleukin 1 alpha and tumor necrosis factor
       alpha, did so. The effect of glutamate appears to be developmentally
       regulated. Indeed, NF-kappa B is found in an inducible form in the
       cytoplasm of neurons of 3- to 7-day-old mice but is constitutively
       activated in the nuclei of neurons derived from older pups (8-10 days
       postnatal). Overall, these observations suggest the existence of a new
       pathway of trans-synaptic regulation of gene expression.
 DE    Aging/*METABOLISM  Animal  Brain/*METABOLISM  Cell Division  Cell
       Nucleus/METABOLISM  Cells, Cultured  Cerebellum/CYTOLOGY/GROWTH &
       DEVELOPMENT/*METABOLISM  Dendrites/METABOLISM/ULTRASTRUCTURE
       Fluorescent Antibody Technique  Glutamic Acid/*PHARMACOLOGY
       Immunohistochemistry  Ligases/METABOLISM  Mice  Neurons/CYTOLOGY/DRUG
       EFFECTS/*METABOLISM  NF-kappa B/ANALYSIS/*METABOLISM  Purkinje
       Cells/CYTOLOGY/METABOLISM  Support, Non-U.S. Gov't  Synapses/*PHYSIOLOGY
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

