REGULATION OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) EXPRESSION ANDRELEASE FROM HIPPOCAMPAL-NEURONS IS MEDIATED BY NON-NMDA TYPE GLUTAMATE RECEPTORS

We have examined the influence of glutamate on cortical brain-derived neurotrophic factor (BDNF) expression using in situ hybridization and immunohistochemistry. Kainic acid (KA) produced an upregulation of hip pocampal and neocortical BDNF mRNA as well as BDNF protein that was bl ocked by a non-NMDA antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX ), but was not affected by the NMDA antagonist 2-amino-7-phosphonohept anoic acid (AP7). Basal levels of BDNF mRNA were not affected by NMDA, DNQX, or AP7 treatment. BDNF protein was also increased after kainate exposure with a spatial and temporal course distinct from that seen f or the expression of BDNF mRNA. A dramatic shift in BDNF immunoreactiv ity (-IR) was observed from intracellular compartments to the neuropil surrounding CA3 pyramidal cells 2-3 hr after KA exposure. This shift in localization of BDNF-IR suggests a constitutive release of BDNF at the level of the cell body and dendrites. Moreover, we have localized mRNAs for full-length and truncated trkB, to a coincident population o f neurons and glia. These data suggest the neurons that produce BDNF a lso express components necessary for a biological response to the same neurotrophic factor. The present study also demonstrates increased BD NF-IR in the messy fiber terminal zone of hippocampus after exposure t o KA, as well as an increase in trkB mRNA, and provides evidence of lo cal release of this neurotrophin into the surrounding neuropil where i t would be available for local utilization. The synthesis and putative release of BDNF from somatic and/or dendritic sites within the hippoc ampus provide evidence of a potential autocrine or paracrine role for BDNF, and establish a local source of trophic support for the maintena nce of synaptic plasticity and anatomic reorganization in the mature n ervous system.