Corticotrophin releasing factor receptor 1 antagonists prevent chronic stress-induced behavioral changes and synapse loss in aged rats. (April 2018)

• Record Type: Journal Article
• Authors: Dong, Hongxin; Keegan, Jack M.; Hong, Ellie; Gallardo, Christopher; Montalvo-Ortiz, Janitza; Wang, Becky; Rice, Kenner C.; Csernansky, John
• Is Part Of: Psychoneuroendocrinology. Volume 90(2018)
• Page Start: 92
• Page End: 101
• Publication Date: 2018-04
• Subjects: Stress -- Aging -- Corticotrophin releasing factor receptor 1 antagonist -- Memory -- Neurodegeneration -- Rats; Psychoneuroendocrinology -- Periodicals; Endocrinology -- Periodicals; Neurology -- Periodicals; Psychiatry -- Periodicals; Neuropsychoendocrinologie -- Périodiques; 616.8
• DOI: 10.1016/j.psyneuen.2018.02.013
• Languages: English
• ISSNs: 0306-4530

Abstract

Highlights: Aged rats display severe behavior deficits and synaptic loss after chronic stress. CRF1 antagonists prevent anxiety-related behaviors and memory deficits in aged rats. CRF1 antagonists restore HPA axis function and prevent synapse loss in stressed aged rats. Abstract: Mounting evidence suggests that chronic stress can alter brain structure and function and promote the development of neuropsychiatric disorders, such as depression and Alzheimer's disease. Although the results of several studies have indicated that aged brains are more vulnerable to chronic stress, it remains unknown whether antagonists of a key stress regulator, the corticotrophin releasing factor receptor 1 (CRF1), can prevent stress-induced anxiety and memory deficits in animal models. In this study, we evaluated the potential benefits of two CRF1 antagonists, R121919 and antalarmin, for preventing stress-induced anxiety-related behavioral and memory deficits and neurodegeneration in aged rats. We stressed rats using isolation-restraint for 3 months starting from the 18 months of age. Subsets of animals were administrated either R121919 or antalarmin through food chow for 3 months, followed by a series of behavioral, biochemical and morphological analyses. We found that stressed aged rats displayed body weight losses and increased corticosterone levels, as well as anxiety-related behaviors and memory deficits. Additionally, chronic stress induced a loss of cortical dendritic spines and synapses. However, R121919 and antalarmin both prevented stress-induced behavioral changes including anxiety-related behaviors and memory deficits and prevented synapse loss, perhaps through reversing HPA axis dysfunction. These results suggest that CRF1 antagonists may hold promise as a potential therapy for preventing stress-induced anxiety and memory deficits in aged individuals.