Brain-derived neurotrophic factor, nerve growth factor and neurotrophin-3 in selected regions of the rat brain following kainic acid-induced seizure activity

Changes in levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3) in various regions of the rat brain following kainic acid-induced seizure activity were investigated. BDNF pro tein, as measured by a two-site enzyme immunoassay, increased transiently 1 2-24 h after the intraperitoneal administration of kainic acid to 61.6 ng/g wet weight in the hippocampus (similar to 10-fold increase), 19.5 ng/g in the piriform plus entorhinal cortex (similar to 10-fold) and 8.2 ng/g in th e olfactory bulb (similar to 16-fold), and then rapidly decreased. Increase s of 2- to 4-fold in levels of BDNF were also detected in the septum, cereb ral cortex, striatum and hypothalamus, but not in the cerebellum. In contra st, levels of NGF and NT-3 decreased 24 h after the administration of kaini c acid. Western and Northern blotting analyses of hippocampal tissues, resp ectively, revealed increase in levels of a 14-kDa protein corresponding to BDNF and its mRNA at both 4.2 and 1.4 kb. Hippocampal mRNAs for NGF and NT- 3 increased and decreased, respectively, in kainic acid-treated rats. Immun ohistological investigations showed that, in the hippocampus, the administr ation of kainic acid enhanced a homogeneous immunoreactivity of BDNF in the polymorph inner layer (the stratum radiatum of the CA3/CA4 regions and the hilar region) and in granule cells of the dentate gyrus. BDNF protein was found in neurons, but not at all in glial cells or in blood vessels, and wa s localized in the cytoplasm, the nucleoplasm and the primary dendrites of neurons as well as in perisynaptic extracellular spaces, but hardly in thei r axons. Our results show that kainic acid treatment increases levels of BD NF, but not NGF or NT-3, in various regions of the rat brain, other than th e cerebellum. Also, the majority of BDNF newly synthesized by hippocampal g ranule neurons is secreted into the perisynaptic extracellular space in the polymorph inner layer of the dentate gyrus, supporting an autocrine-like r ole for the factor in synaptic functions. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.