TY - JOUR
T1 - Evidence of lasting dysregulation of neuroendocrine and HPA axis function following global cerebral ischemia in male rats and the effect of Antalarmin on plasma corticosterone level
AU - De la Tremblaye, Patricia B.
AU - Raymond, Julie
AU - Milot, Marc R.
AU - Merali, Zul
AU - Plamondon, Hélène
N1 - Funding Information:
The authors thank Sylvie Emond and Jon James for excellent technical assistance in the animal facility and in conducting the CORT RIA assessments, respectively. We are also grateful to Dr. Alfonso Abizaid for his assistance in troubleshooting the CRH antibody for immunohistochemical analysis and Dr. Pam Kent for comments on the manuscript. This work was supported by a grant from the National Science and Engineering Research Council of Canada to Hélène Plamondon and internal funding from the University of Ottawa . The authors declare having no conflict of interest regarding the work described here.
PY - 2014/3
Y1 - 2014/3
N2 - Abnormal function of the neuroendocrine stress system has been implicated in the behavioral impairments observed following brain ischemia. The current study examined long-term changes in stress signal regulation 30. days following global cerebral ischemia. Experiment 1 investigated changes in the expression of corticotropin releasing hormone (CRH) and its subtype 1 receptor (CRHR1), glucocorticoid receptors (GR) in the paraventricular nucleus of the hypothalamus (PVN), the central nucleus of the amygdala (CeA), and the CA1 subfield of the hippocampus. Tyrosine hydroxylase (TH) was determined at the locus coeruleus (LC). Experiment 2 investigated the role of central CRHR1 activation on corticosterone (CORT) secretion at multiple time intervals following global ischemia after exposure to an acute stressor. Findings from Experiment 1 demonstrated a persistent increase in GR, CRH and CRHR1 immunoreactivity (ir) at the PVN, reduced GR and CRHR1 expression in pyramidal CA1 neurons, and increased LC TH expression in ischemic rats displaying working memory errors in the radial arm Maze. Findings from Experiment 2 revealed increased CORT secretion up to 7. days, but no longer present 14 and 21. days post ischemia. However upon an acute restraint stress induced 27. days following reperfusion, ischemic rats had increased plasma CORT secretions compared to sham-operated animals, suggesting HPA axis hypersensitivity. Antalarmin (2. μg/2. μl) pretreatment significantly attenuated post ischemic elevation of basal and stress-induced CORT secretion. These findings support persistent neuroendocrine dysfunctions following brain ischemia likely to contribute to emotional and cognitive impairments observed in survivors of cardiac arrest and stroke.
AB - Abnormal function of the neuroendocrine stress system has been implicated in the behavioral impairments observed following brain ischemia. The current study examined long-term changes in stress signal regulation 30. days following global cerebral ischemia. Experiment 1 investigated changes in the expression of corticotropin releasing hormone (CRH) and its subtype 1 receptor (CRHR1), glucocorticoid receptors (GR) in the paraventricular nucleus of the hypothalamus (PVN), the central nucleus of the amygdala (CeA), and the CA1 subfield of the hippocampus. Tyrosine hydroxylase (TH) was determined at the locus coeruleus (LC). Experiment 2 investigated the role of central CRHR1 activation on corticosterone (CORT) secretion at multiple time intervals following global ischemia after exposure to an acute stressor. Findings from Experiment 1 demonstrated a persistent increase in GR, CRH and CRHR1 immunoreactivity (ir) at the PVN, reduced GR and CRHR1 expression in pyramidal CA1 neurons, and increased LC TH expression in ischemic rats displaying working memory errors in the radial arm Maze. Findings from Experiment 2 revealed increased CORT secretion up to 7. days, but no longer present 14 and 21. days post ischemia. However upon an acute restraint stress induced 27. days following reperfusion, ischemic rats had increased plasma CORT secretions compared to sham-operated animals, suggesting HPA axis hypersensitivity. Antalarmin (2. μg/2. μl) pretreatment significantly attenuated post ischemic elevation of basal and stress-induced CORT secretion. These findings support persistent neuroendocrine dysfunctions following brain ischemia likely to contribute to emotional and cognitive impairments observed in survivors of cardiac arrest and stroke.
KW - CRHR1
KW - Corticotropin releasing hormone
KW - Global cerebral ischemia
KW - Glucocorticoid receptors
KW - HPA dysregulation
KW - Immunohistochemistry
KW - Rat
UR - https://www.scopus.com/pages/publications/84896839548
U2 - 10.1016/j.yhbeh.2014.01.003
DO - 10.1016/j.yhbeh.2014.01.003
M3 - Article
C2 - 24444675
AN - SCOPUS:84896839548
SN - 0018-506X
VL - 65
SP - 273
EP - 284
JO - Hormones and Behavior
JF - Hormones and Behavior
IS - 3
ER -