Abstract

The corticotropin releasing hormone receptors (CRHR) and their endogenous ligands coordinate the human response to acute or chronic stressful stimuli. While the appropriate response to acute stressors (fight or flight) can be life-saving, chronic stress is almost always harmful. Prior work has shown that ageing increases the susceptibility to stress. We studied the question of whether antagonism of corticotropin releasing hormone receptor 1 can prevent can prevent stress-induced anxiety and memory loss in rats. We used R121919 and antalarmin as nonpeptide antagonists in an isolation-restraint stress paradigm for 3 months. Rats received either R121919 or antalarmin in food chow or only food chow. Untreated aged rats showed weight loss, elevated corticosterone levels and anxiety-related behaviors and loss of cortical synapses as expected. Both R121919 and antalarmin prevented the effects observed in the untreated rats. Our results suggest that antagonism of the CHR stress system can mitigate the advance of Alzheimer's-likedisease in this model and that CRH antagonists may be useful as medications to blunt the advance of Alzheimer's disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIADA000528-11
Application #
9785195
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2018
Total Cost
Indirect Cost

  Institution

Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Dong, Hongxin; Keegan, Jack M; Hong, Ellie et al. (2018) Corticotrophin releasing factor receptor 1 antagonists prevent chronic stress-induced behavioral changes and synapse loss in aged rats. Psychoneuroendocrinology 90:92-101
Micioni Di Bonaventura, Maria Vittoria; Ubaldi, Massimo; Giusepponi, Maria Elena et al. (2017) Hypothalamic CRF1 receptor mechanisms are not sufficient to account for binge-like palatable food consumption in female rats. Int J Eat Disord 50:1194-1204
Zhang, Cheng; Kuo, Ching-Chang; Moghadam, Setareh H et al. (2016) Corticotropin-releasing factor receptor-1 antagonism mitigates beta amyloid pathology and cognitive and synaptic deficits in a mouse model of Alzheimer's disease. Alzheimers Dement 12:527-37
Pomrenze, Matthew B; Millan, E Zayra; Hopf, F Woodward et al. (2015) A Transgenic Rat for Investigating the Anatomy and Function of Corticotrophin Releasing Factor Circuits. Front Neurosci 9:487
Zhang, Cheng; Kuo, Ching-Chang; Moghadam, Setareh H et al. (2015) Corticotropin-Releasing Factor Receptor-1 Antagonism Reduces Oxidative Damage in an Alzheimer’s Disease Transgenic Mouse Model. J Alzheimers Dis 45:639-50
Northcutt, A L; Hutchinson, M R; Wang, X et al. (2015) DAT isn't all that: cocaine reward and reinforcement require Toll-like receptor 4 signaling. Mol Psychiatry 20:1525-37
Campbell, Shannon N; Zhang, Cheng; Monte, Louise et al. (2015) Increased tau phosphorylation and aggregation in the hippocampus of mice overexpressing corticotropin-releasing factor. J Alzheimers Dis 43:967-76
Dong, Hongxin; Wang, Shirlene; Zeng, Ziling et al. (2014) Effects of corticotrophin-releasing factor receptor 1 antagonists on amyloid-? and behavior in Tg2576 mice. Psychopharmacology (Berl) 231:4711-22
Micioni Di Bonaventura, Maria Vittoria; Ciccocioppo, Roberto; Romano, Adele et al. (2014) Role of bed nucleus of the stria terminalis corticotrophin-releasing factor receptors in frustration stress-induced binge-like palatable food consumption in female rats with a history of food restriction. J Neurosci 34:11316-24
Iemolo, Attilio; Blasio, Angelo; St Cyr, Stephen A et al. (2013) CRF-CRF1 receptor system in the central and basolateral nuclei of the amygdala differentially mediates excessive eating of palatable food. Neuropsychopharmacology 38:2456-66

Showing the most recent 10 out of 18 publications