Sustained corticosterone rise in the prefrontal cortex is a key factor for chronic stress-induced working memory deficits in mice

Publication date: Available online 4 April 2019Source: Neurobiology of StressAuthor(s): Dominguez Gaelle, Henkous Nadia, Prevot Thomas, David Vincent, Guillou Jean-Louis, Belzung Catherine, Mons Nicole, Béracochéa DanielAbstractExposure to prolonged, unpredictable stress leads to glucocorticoids-mediated long-lasting neuroendocrine abnormalities associated with emotional and cognitive impairments. Excessive levels of serum glucocorticoids (cortisol in humans, corticosterone in rodents) contribute notably to deficits in working memory (WM), a task which heavily relies on functional interactions between the medial prefrontal cortex (PFC) and the dorsal hippocampus (dHPC). However, it is unknown whether stress-induced increases in plasma corticosterone mirror corticosterone levels in specific brain regions critical for WM. After a 6 week-UCMS exposure, C57BL/6 J male mice exhibited increased anxiety- and depressive-like behaviors when measured one week later and displayed WM impairments timely associated with increased plasma corticosterone response. In chronically stressed mice, basal phosphorylated/activated CREB (pCREB) was markedly increased in the PFC and the CA1 area of the dHPC and WM testing did not elicit any further increase in pCREB in the two regions. Using microdialysis samples from freely-moving mice, we found that WM testing co-occurred with a rapid and sustained increase in corticosterone response in the PFC while there was a late, non-significant rise of cor...
Source: Neurobiology of Stress - Category: Neuroscience Source Type: research