STIMULATION OF IONOTROPIC GLUTAMATE RECEPTORS ACTIVATES TRANSCRIPTIONFACTOR NF-KAPPA-B IN PRIMARY NEURONS

L-Glutamate is the most common excitatory neurotransmitter in the brai n and plays a crucial role in neuronal plasticity as well as in neurot oxicity. While a large body of literature describes the induction of i mmediate-early genes, including c-fos, fosB, c-jun, junB, zif/268, and krox genes by glutamate and agonists in neurons, very little is known about preexisting transcription factors controlling the induction of such genes. This prompted us to investigate whether stimulation of glu tamate receptors can activate NF-kappa B, which is present in neurons in either inducible or constitutive form. Here we report that brief tr eatments with kainate or high potassium strongly activated NF-kappa B in granule cells from rat cerebellum. This was detected at the single cell level by immunostaining with a monoclonal antibody that selective ly reacts with the transcriptionally active, nuclear form of NF-kappa B p65. The activation of NF-kappa B could be blocked with the antioxid ant pyrrolidine dithiocarbamate, suggesting the involvement of reactiv e oxygen intermediates, The data may explain the kainate-induced cell surface expression of major histocompatibility complex class I molecul es, which are encoded by genes known to be controlled by NF-kappa B. M oreover, NF-kappa B activity was found to change dramatically in neuro ns during development of the cerebellum between days 5 and 7 after bir th.