Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1995 Sep 26;92(20):9077-81.
doi: 10.1073/pnas.92.20.9077.

Synaptic activation of NF-kappa B by glutamate in cerebellar granule neurons in vitro

Affiliations

Synaptic activation of NF-kappa B by glutamate in cerebellar granule neurons in vitro

L Guerrini et al. Proc Natl Acad Sci U S A. .

Abstract

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.

PubMed Disclaimer

Similar articles

Cited by

References

    1. J Comp Neurol. 1971 Mar;141(3):283-312 - PubMed
    1. J Biol Chem. 1995 Feb 10;270(6):2703-7 - PubMed
    1. Nature. 1987 Apr 16-22;326(6114):711-3 - PubMed
    1. J Neurosci. 1987 Jun;7(6):1928-34 - PubMed
    1. Nature. 1989 Jun 29;339(6227):701-3 - PubMed

Publication types

MeSH terms