title: Corticotropin-releasing hormone heterogeneous nuclear RNA (hnRNA) and immunoreactivity are induced in extrahypothalamic brain sites by kainic-acid-induced seizures and are modulated by estrogen.
abstract: Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are pivotal mediators of the hormonal response to stressors and are found within neurons of the paraventricular nucleus of the hypothalamus (PVN) and several extrahypothalamic sites where expression is activity-dependent. Previous work has shown increased CRH immunoreactivity in extrahypothalamic sites after kainic-acid (KA)-induced seizures in male rats. This study examined the induction of CRH heterogeneous nuclear RNA (hnRNA), AVP hnRNA and c-fos as a measure of gene transcription and cell activation following kainic-acid (KA)-induced seizures. KA or saline was administered to intact male rats, ovariectomized (OVX) females and OVX females treated with 17beta-estradiol (E2). Animals were sacrificed 0, 15, 60 or 120 min following KA treatment. In the PVN, CRH hnRNA levels were increased by KA treatment at 15, 60, and 120 min. AVP hnRNA and c-fos mRNA in the PVN were also significantly elevated above controls at all time points. Elevations in CRH hnRNA were also identified in hippocampus, the lateral bed nucleus of the stria terminalis (BNST) and globus pallidus at 60 and 120 min following KA and in the piriform cortex, and central nucleus of the amygdala at 120 min after KA. CRH hnRNA levels at 120 min in the PVN, amygdala, cingulate cortex, hippocampus (CA1), piriform cortex, and BNST were lower in OVX+E2 females compared to females without E2. To determine if the increases in CRH hnRNA translated to increased CRH peptide, immunocytochemistry was performed. CRH immunoreactivity was increased in the amygdala, BNST, cingulate cortex, PVN and globus pallidus within 3 h after KA treatment and in the piriform cortex and hippocampus by 6 h after KA. These results suggest a time-dependent activation of the CRH system following activation of kainate receptors, which may result in long-term changes in the expression of extrahypothalamic CRH.
authors.affiliation: Department of Biomedical Sciences, Anatomy and Neurobiology Section, Colorado State University, Fort Collins, CO 80523, USA. Chad.Foradori@colostate.edu
authors.forename: Chad D
authors.initials: CD
authors.lastname: Foradori
authors.forename: Trent D
authors.initials: TD
authors.lastname: Lund
authors.forename: Alan H
authors.initials: AH
authors.lastname: Nagahara
authors.forename: James I
authors.initials: JI
authors.lastname: Koenig
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Handa
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D003292:Convulsants; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics*; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D007150:Immunohistochemistry; D007608:Kainic Acid; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D003292:Convulsants; D004967:Estrogens; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D001127:Arginine Vasopressin; D004958:Estradiol; D003346:Corticotropin-Releasing Hormone; D007608:Kainic Acid