Hippocampal extracellular matrix alterations contribute to cognitive impairment associated with a chronic depressive-like state in rats

Danai Riga, Ioannis Kramvis, Maija K. Koskinen, Pieter Van Bokhoven, Johanneke E. Van Der Harst, Tim S. Heistek, A. Jaap Timmerman, Pim Van Nierop, Roel C. Van Der Schors, Anton W. Pieneman, Anouk De Weger, Yvar Van Mourik, Anton N.M. Schoffelmeer, Huib D. Mansvelder, Rhiannon M. Meredith, Witte J.G. Hoogendijk, August B. Smit, Sabine Spijker*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Patients with depression often suffer from cognitive impairments that contribute to disease burden. We used social defeat–induced persistent stress (SDPS) to induce a depressive-like state in rats and then studied long-lasting memory deficits in the absence of acute stressors in these animals. The SDPS rat model showed reduced short-term object location memory and maintenance of long-term potentiation (LTP) in CA1 pyramidal neurons of the dorsal hippocampus. SDPS animals displayed increased expression of synaptic chondroitin sulfate proteoglycans in the dorsal hippocampus. These effects were abrogated by a 3-week treatment with the antidepressant imipramine starting 8 weeks after the last defeat encounter. Next, we observed an increase in the number of perineuronal nets (PNNs) surrounding parvalbumin-expressing interneurons and a decrease in the frequency of inhibitory postsynaptic currents (IPSCs) in the hippocampal CA1 region in SDPS animals. In vivo breakdown of the hippocampus CA1 extracellular matrix by the enzyme chondroitinase ABC administered intracranially restored the number of PNNs, LTP maintenance, hippocampal inhibitory tone, and memory performance on the object place recognition test. Our data reveal a causal link between increased hippocampal extracellular matrix and the cognitive deficits associated with a chronic depressive-like state in rats exposed to SDPS.

Original languageEnglish
Article numbereaai8753
JournalScience Translational Medicine
Volume9
Issue number421
DOIs
Publication statusPublished - 20 Dec 2017

Cite this

Riga, D., Kramvis, I., Koskinen, M. K., Van Bokhoven, P., Van Der Harst, J. E., Heistek, T. S., ... Spijker, S. (2017). Hippocampal extracellular matrix alterations contribute to cognitive impairment associated with a chronic depressive-like state in rats. Science Translational Medicine, 9(421), [eaai8753]. https://doi.org/10.1126/scitranslmed.aai8753