Amygdaloid pERK1/2 in corticotropin-releasing hormone overexpressing mice under basal and acute stress conditions.
Corticotropin-releasing hormone (CRH) coordinates neuroendocrine and behavioral adaptations to stress. Acute CRH administration in vivo activates extracellular signal-regulated kinase 1/2 (ERK1/2) in limbic brain areas, acting through the CRH receptor type 1 (CRH-R1). In the present study, we used CRH-COE-Cam mice that overexpress CRH in limbic-restricted areas, to analyze the effect of chronic CRH overexpression on ERK1/2 activation. By immunohistochemistry and confocal microscopy analysis we found that pERK1/2 levels in the basolateral amygdala (BLA) were similar in control and CRH overexpressing mice under basal conditions. Acute stress caused comparably increased levels of corticosterone in both control (CRH-COEcon-Cam) and CRH overexpressing (CRH-COEhom-Cam) animals. CRH-COEhom-Cam mice after stress showed reduced pERK1/2 immunoreactivity in the BLA compared to CRH-COEhom-Cam animals under basal conditions. Radioligand binding and in situ hybridization revealed higher density of CRH-R1 in the amygdala of CRH-COEhom mice under basal conditions compared to control littermates. A significant reduction of the receptor levels was observed in this area after acute stress, suggesting that stress may trigger CRH-R1 internalization/downregulation in these CRH overexpressing mice. Chronic CRH overexpression leads to reduced ERK1/2 activation in response to acute stress in the BLA.
Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología y Biología y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and IFIBYNE-CONICET, Ciudad Universitaria, Buenos Aires, Argenita.
S
S
Silberstein
A M
AM
Vogl
D
D
Refojo
S A
SA
Senin
W
W
Wurst
F
F
Holsboer
J M
JM
Deussing
E
E
Arzt
D029845:Amphibian Proteins / Q000378:metabolism; D000679:Amygdala / Q000201:enzymology*; D000818:Animals; D001345:Autoradiography; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology*; D007456:Iodine Isotopes / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D036361:Peptide Hormones / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D011863:Radioimmunoassay; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists / Q000378:metabolism*; D012149:Restraint, Physical / Q000379:methods; D013315:Stress, Psychological / Q000201:enzymology / Q000209:etiology / Q000473:pathology*; D013997:Time Factors
D029845:Amphibian Proteins; D007456:Iodine Isotopes; D036361:Peptide Hormones; D018019:Receptors, Corticotropin-Releasing Hormone; C025727:sauvagine; D003346:Corticotropin-Releasing Hormone; D048052:Mitogen-Activated Protein Kinase 3; D003345:Corticosterone