In vivo regulation of glial cell line-derived neurotrophic factor-inducible transcription factor by kainic acid

A putative transcription factor induced in vitro by glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor-beta was recentl y cloned and characterized [Yajima S, er al. (1997) J. Neurosci. 17, 8657-8 666]. The messenger RNA of this protein, termed murine GDNF-inducible trans cription factor (mGIF, hereafter referred to as GIF), is localized within c ortical and hippocampal regions of brain, suggesting that GIF might be regu lated by perturbations of these brain regions. In an effort to learn more a bout the role of GIF in vivo, we examined GIF messenger RNA in the brains o f rats treated with the glutamatergic agonist kainic acid. This treatment i s known to induce seizures and alter the messenger RNA expression of severa l growth factors, including GDNF, in several brain regions. Rats were given intraperitoneal saline (1 ml/kg) or kainic acid (15 mg/kg) and were killed at various time-points for in situ hybridization of brain sections with a GIF messenger RNA riboprobe. In saline-treated rats, GIF messenger RNA was present at low levels in cerebral colter, hippocampus and hippocampal remna nts such as the taenia tecta. Kainic acid treatment induced robust increase s in GIF messenger RNA in several brain regions, including cerebral cortex, hippocampus, caudate-putamen, nucleus accumbens, and several nuclei of the amygdala and hypothalamus. Most brain regions showed the greatest increase in GIF messenger RNA 4-6 h after kainic acid administration and a return t owards normal levels at 48 h. The CA3 region of hippocampus, however, showe d a more rapid increase in GIF messenger RNA that was also evident 48 h aft er kainic acid administration. These results demonstrate that GIF messenger RNA can be regulated in vivo, and that this novel factor warrants further study as a central mediator of GDNF and perhaps other neurotrophic factors. (C) 1999 IBRO. Published by El sevier Science Ltd.