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sst-receptor gene deletion exacerbates chronic stress-induced deficits: Consequences for emotional and cognitive ageing
- Source :
- Progress in Neuro-Psychopharmacology and Biological Psychiatry. 86:390-400
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- This study investigated whether sst2 gene deletion interacts with age and chronic stress exposure to produce exacerbated emotional and cognitive ageing. Middle-aged (10–12 month) sst2 knockout (sst2KO) and wild-type (WT) mice underwent an unpredictable chronic mild stress (UCMS) procedure for 6 weeks or no stress for control groups. This was followed by a battery of tests to assess emotional and cognitive functions and neuroendocrine status (CORT level). A re-evaluation was performed 6 months later (i.e. with 18-month-old mice). UCMS reproduced neuroendocrine and behavioral features of stress-related disorders such as elevated circulating CORT levels, physical deteriorations, increased anxiety- and depressive-like behaviors and working memory impairments. sst2KO mice displayed behavioral alterations which were similar to stressed WT and exhibited exacerbated changes following UCMS exposure. The evaluations performed in the older mice showed significant long-term effects of UCMS exposure. Old sst2KO mice previously exposed to UCMS exhibited spatial learning and memory accuracy impairments and high levels of anxiety-like behaviors which drastically added to the effects of normal ageing. Spatial abilities and emotionality scores (mean z-scores) measured both at the UCMS outcome and 6 months later were correlated with the initially measured CORT levels in middle-age. The present findings indicate that the deletion of the sst2 receptor gene produces chronic hypercorticosteronemia and exacerbates sensitivity to stressors which over time, have consequences on ageing brain function processes.
- Subjects :
- 0301 basic medicine
Pharmacology
medicine.medical_specialty
Working memory
business.industry
Stressor
Cognition
03 medical and health sciences
chemistry.chemical_compound
030104 developmental biology
0302 clinical medicine
Endocrinology
chemistry
Corticosterone
Emotionality
Ageing
Internal medicine
medicine
Anxiety
Chronic stress
medicine.symptom
business
030217 neurology & neurosurgery
Biological Psychiatry
Subjects
Details
- ISSN :
- 02785846
- Volume :
- 86
- Database :
- OpenAIRE
- Journal :
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Accession number :
- edsair.doi...........cca63b01cbd8c3643a24015af51e1e12