Restraint-induced fra-2 and c-fos expression in the rat forebrain: Relationship to stress duration

• Published in: Neuroscience Vol. 150; no. 2; pp. 478 - 486
• Main Authors: Weinberg, M.S, Girotti, M, Spencer, R.L
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 05.12.2007; Elsevier
• Subjects: ACTH; Adrenocorticotropic Hormone - blood; Adrenocorticotropic Hormone - secretion; Animals; Biological and medical sciences; CORT; Fos-Related Antigen-2 - genetics; Fos-Related Antigen-2 - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - genetics; Hydrocortisone - blood; Hydrocortisone - secretion; Hypothalamo-Hypophyseal System - metabolism; Hypothalamo-Hypophyseal System - physiopathology; Hypothalamo-Hypophyseal System - secretion; hypothalamus–pituitary–adrenal axis; IEG; In Situ Hybridization; Male; Neurology; Neuronal Plasticity - genetics; Pituitary-Adrenal System - metabolism; Pituitary-Adrenal System - physiopathology; Pituitary-Adrenal System - secretion; Prosencephalon - anatomy & histology; Prosencephalon - metabolism; Prosencephalon - physiopathology; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Sprague-Dawley; Restraint, Physical; RNA, Messenger - analysis; RNA, Messenger - metabolism; Stress, Psychological - genetics; Stress, Psychological - metabolism; Stress, Psychological - physiopathology; Time Factors; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - metabolism; Transcriptional Activation; Vertebrates: nervous system and sense organs; prefrontal cortex; LS; ACTH; PVN; cyclic AMP binding protein response element; cAMP; PFC; AP-1; analysis of variance; hypothalamus–pituitary–adrenal axis; ANOVA; adrenal corticotropin hormone; cyclic AMP; prelimbic prefrontal cortex; infralimbic prefrontal cortex; IL; IEG; activating protein-1; lateral septum; paraventricular nucleus of the hypothalamus; ROI; CORT; hypothalamus–pituitary–adrenal; CRE; region of interest; HPA; immediate-early gene; VO; corticosterone; PL; ventral orbital prefrontal cortex; hypothalamus-pituitary-adrenal axis; Rat; fos Gene; Rodentia; Central nervous system; Duration; Hypothalamus; Gene expression; Stress; Encephalon; Prosencephalon; Vertebrata; Mammalia; Adrenocorticotropic hormone; Adenohypophyseal hormone; Animal; Pituitary gland; Protooncogene; Immediate early gene
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2007.09.013

Abstract The protein product of the fra-2 gene (Fra-2), a fos -family member, can compete with Fos protein for participation in activating protein-1 (AP-1) transcription factor complexes and each protein can contribute different transactivational consequences to an AP-1 complex. To date, there is limited characterization of fra-2 mRNA expression in the rat forebrain. We examined basal and restraint-induced mRNA expression ( in situ hybridization) of fra-2 in the rat forebrain and compared its temporal–spatial pattern to c-fos . In contrast to the very low basal expression of c-fos , fra-2 basal expression was moderately high throughout cortex and some subcortical structures, including prominent basal expression in the hypothalamic paraventricular nucleus (PVN). Restraint-induced fra-2 expression was quantified in the prefrontal cortex (PFC), lateral septum (LS) and PVN. Maximal fra-2 gene induction in the PFC and LS was delayed (60 min) after restraint onset with respect to c-fos (15 min), whereas in the PVN, fra-2 mRNA increased within 15 min of restraint. Additionally we compared c-fos and fra-2 gene expression in rats given shorter or longer restraint durations, but equal total time from stress onset to sample collection, to determine the extent to which the kinetics of gene induction matched that of a hypothalamic–pituitary–adrenal axis hormone response. Rats given 45 min recovery after 15 min restraint showed less c-fos expression in the PVN, less fra-2 expression in the prelimbic and infralimbic PFC, and no difference in the LS compared with rats restrained for 60 min. Thus, the expression of both genes was sensitive to stressor duration, but this sensitivity varied with brain region. Differential basal and stress-induced expression patterns of the fra-2 and c-fos genes are likely to have important functional consequences for AP-1 transcription factor dependent regulation of neural plasticity.