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

Maija Kreetta Koskinen, Yvar van Mourik, August Benjamin Smit, Danai Riga, Sabine Spijker*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


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.

Original languageEnglish
Article number17308
Pages (from-to)1-12
Number of pages12
JournalScientific Reports
Publication statusPublished - 14 Oct 2020


DR and ABS received support from NBSIK PharmaPhenomics grant LSH framework FES0908; MKK, DR, and SS were supported by an NWO VICI grant (ALW-Vici 016.150.673/865.14.002); DR was supported by the EU Research and Innovation Framework Programme Horizon 2020: Marie Skłodowska Curie Actions, Individual Fellowship (MSCA-IF-EF-ST; 793106).

FundersFunder number
Horizon 2020 Framework Programme
H2020 Marie Skłodowska-Curie Actions793106
Nederlandse Organisatie voor Wetenschappelijk OnderzoekALW-Vici 016.150.673/865.14.002


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