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From stress to depression: development of extracellular matrix-dependent cognitive impairment following social stress.

ABSTRACT: Stress can predispose to depressive episodes, yet the molecular mechanisms regulating the transition from the initial stress response to a persistent pathological depressive state remain poorly understood. We profiled the development of an enduring depressive-like state by assessing affective behavior and hippocampal function during the 2 months following social-defeat stress. We measured remodeling of hippocampal extracellular matrix (ECM) during this period, as we recently identified ECM changes to mediate cognitive impairment during the sustained depressive-like state. Affective disturbance and cognitive impairments develop disparately after social stress, with gradual appearance of affective deficits. In contrast, spatial memory was impaired both early after stress and during the late-emerging chronic depressive-like state, while intact in-between. Similarly, we observed a biphasic regulation of the hippocampal ECM coinciding with hippocampus-dependent memory deficits. Together our data (1) reveal a dichotomy between affective and cognitive impairments similar to that observed in patients, (2) indicate different molecular processes taking place during early stress and the chronic depressive-like state, and (3) support a role of the ECM in mediating long-lasting effects on memory. From a translational point of view, it is important to prioritize on temporal phenotypic aspects in animal models to elucidate the underlying mechanisms of depression.

SUBMITTER: Koskinen MK

PROVIDER: S-EPMC7560730 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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From stress to depression: development of extracellular matrix-dependent cognitive impairment following social stress.

Koskinen Maija-Kreetta MK van Mourik Yvar Y Smit August Benjamin AB Riga Danai D Spijker Sabine S

Scientific reports 20201014 1

Stress can predispose to depressive episodes, yet the molecular mechanisms regulating the transition from the initial stress response to a persistent pathological depressive state remain poorly understood. We profiled the development of an enduring depressive-like state by assessing affective behavior and hippocampal function during the 2 months following social-defeat stress. We measured remodeling of hippocampal extracellular matrix (ECM) during this period, as we recently identified ECM chang ...[more]

PMID: 33057053

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Project description:BackgroundExisting estimates of the impact of the COVID-19 burden on mental wellbeing come from countries with high mortality rates. This study therefore aimed to investigate the impact of the first COVID-19 lockdown (March-April 2020) on risk for stress/depression and functional impairment in a representative sample of adult individuals in Denmark, which had lower infection rates, and whether the impact of lockdown was heterogeneous across living situation.MethodsUsing a representative, randomly drawn sample from the complete Danish adult population interviewed in March 2 to April 13, 2020 (n = 2836) and again in July 2020 (n = 1526, 54% retention rate), we study how the imposed lockdown announced March 11 following the onset of the first Danish wave of COVID-19 infections affected mental wellbeing. We use the World Health Organization Five Well-being Index (WHO-5) and the Work and Social Adjustment Scale (WSAS) to capture risk for stress/depression (WHO-5 < 50) and functional impairment (WSAS > 10). Using covariate adjusted ordinary least squares linear probability models and exploiting variation in the timing of responses occurring just before and just after the introduction of lockdown, we compare respondents before lockdown to respondents that answered during lockdown, as well as to answers in re-interviews in July.ResultsIn our fully controlled models, we find reduced depressive symptoms among adults immediately after the shutdown, concentrated in adults with children living at home (-.089, p < .01 (from pre lockdown baseline .273)). Measures of functional impairment also declined immediately after the March shutdown among adults with children living at home (-.066, p < .05 (from pre lockdown baseline .150)). Impairment intensified for the entire sample between March and July (+.199, p < .001 (from pre lockdown baseline .248)), but depressive symptoms remained at lower rate in July (-.033, p < .05 (from pre lockdown baseline .332).ConclusionsFindings in Denmark indicate that living with children at home may have, in the short term, buffered the potential mental health sequelae of the COVID-19 shutdown.

Dataset Information

From stress to depression: development of extracellular matrix-dependent cognitive impairment following social stress.

Publications

From stress to depression: development of extracellular matrix-dependent cognitive impairment following social stress.

Similar Datasets

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