EXPRESSION OF BRAIN-DERIVED NEUROTROPHIC FACTOR PROTEIN IN THE ADULT-RAT CENTRAL-NERVOUS-SYSTEM

We have generated and characterized a multi-functional polyclonal anti -brain-derived neurotrophic factor antibody. Western blot analysis, do rsal root ganglion neurite outgrowth and dorsal root ganglion neuron s urvival assays showed that this antibody specifically recognized brain -derived neurotrophic factor and not the other neurotrophins. Furtherm ore, it was capable of blocking the functional effects of brain-derive d neurotrophic factor. Using this antibody, we examined the expression of brain-derived neurotrophic factor in adult rat brains by immunohis tochemistry. We found distinct brain-derived neurotrophic factor immun oreactivity in several structures of the brain. These included the neo cortex, piriform cortex, amygdaloid complex, hippocampal formation, cl austrum, some thalamic and hypothalamic nuclei, the substantia nigra a nd some brainstem structures. In contrast to brain-derived neurotrophi c Factor messenger RNA expression, brain-derived neurotrophic factor i mmunoreactivity was also found in the lateral septum, bed nucleus of t he stria teminalis, medial preoptic nucleus, olivery pretectal nucleus , lateral paragigantocellular nucleus and the dorsal horn of the spina l cord. In normal adult rat brains, there was little or no staining in the CA1 region or the granule cell layer of the dentate gyrus of the hippocampus. However, kainate treatments greatly increased brain-deriv ed neurotrophic factor immunoreactivity in the pyramidal cells of the CAI region, as well as in the dentate gyrus, CA2 and CA3 hippocampal r egions. We present evidence for both the subcellular localization and anterograde transport of endogenous brain-derived neurotrophic factor in the central nervous system. The detection of brain-derived neurotro phic factor protein in several discrete regions of the adult brain, an d brain-derived neurotrophic factor's dramatic up-regulation following kainate treatment, strongly supports a role of brain-derived neurotro phic factor in the maintenance of adult neurons and synapses. Since se veral populations of neurons lost during neurodegenerative diseases sy nthesize brain-derived neurotrophic factor protein, modulation of brai n-derived neurotrophic factor levels may be clinically beneficial. The antibody described in this paper will be helpful in determining more precisely the functional activities of brain-derived neurotrophic fact or in the adult. (C) 1997 IBRO. Published by Elsevier Science Ltd.