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

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
JournalScience Translational Medicine
Volume9
Issue number421
DOIs
Publication statusPublished - 20 Dec 2017

Fingerprint

Extracellular Matrix
Hippocampus
Long-Term Potentiation
Chondroitin ABC Lyase
Chondroitin Sulfate Proteoglycans
Hippocampal CA1 Region
Parvalbumins
Inhibitory Postsynaptic Potentials
Pyramidal Cells
Imipramine
Memory Disorders
Interneurons
Antidepressive Agents
Maintenance
Depression
Enzymes
Cognitive Dysfunction
Therapeutics
Recognition (Psychology)

Keywords

  • Journal Article

Cite this

Riga, Danai ; Kramvis, Ioannis ; Koskinen, Maija K ; van Bokhoven, Pieter ; van der Harst, Johanneke E ; Heistek, Tim S ; Jaap Timmerman, A ; van Nierop, Pim ; van der Schors, Roel C ; Pieneman, Anton W ; de Weger, Anouk ; van Mourik, Yvar ; Schoffelmeer, Anton N M ; Mansvelder, Huib D ; Meredith, Rhiannon M ; Hoogendijk, Witte J G ; Smit, August B ; Spijker, Sabine. / Hippocampal extracellular matrix alterations contribute to cognitive impairment associated with a chronic depressive-like state in rats. In: Science Translational Medicine. 2017 ; Vol. 9, No. 421.
@article{f1de37d8ebf949f6885949cf2d596a88,
title = "Hippocampal extracellular matrix alterations contribute to cognitive impairment associated with a chronic depressive-like state in rats",
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.",
keywords = "Journal Article",
author = "Danai Riga and Ioannis Kramvis and Koskinen, {Maija K} and {van Bokhoven}, Pieter and {van der Harst}, {Johanneke E} and Heistek, {Tim S} and {Jaap Timmerman}, A and {van Nierop}, Pim and {van der Schors}, {Roel C} and Pieneman, {Anton W} and {de Weger}, Anouk and {van Mourik}, Yvar and Schoffelmeer, {Anton N M} and Mansvelder, {Huib D} and Meredith, {Rhiannon M} and Hoogendijk, {Witte J G} and Smit, {August B} and Sabine Spijker",
note = "Copyright {\circledC} 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",
year = "2017",
month = "12",
day = "20",
doi = "10.1126/scitranslmed.aai8753",
language = "English",
volume = "9",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "421",

}

Hippocampal extracellular matrix alterations contribute to cognitive impairment associated with a chronic depressive-like state in rats. / Riga, Danai; Kramvis, Ioannis; Koskinen, Maija K; van Bokhoven, Pieter; van der Harst, Johanneke E; Heistek, Tim S; Jaap Timmerman, A; van Nierop, Pim; van der Schors, Roel C; Pieneman, Anton W; de Weger, Anouk; van Mourik, Yvar; Schoffelmeer, Anton N M; Mansvelder, Huib D; Meredith, Rhiannon M; Hoogendijk, Witte J G; Smit, August B; Spijker, Sabine.

In: Science Translational Medicine, Vol. 9, No. 421, 20.12.2017.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Hippocampal extracellular matrix alterations contribute to cognitive impairment associated with a chronic depressive-like state in rats

AU - Riga, Danai

AU - Kramvis, Ioannis

AU - Koskinen, Maija K

AU - van Bokhoven, Pieter

AU - van der Harst, Johanneke E

AU - Heistek, Tim S

AU - Jaap Timmerman, A

AU - van Nierop, Pim

AU - van der Schors, Roel C

AU - Pieneman, Anton W

AU - de Weger, Anouk

AU - van Mourik, Yvar

AU - Schoffelmeer, Anton N M

AU - Mansvelder, Huib D

AU - Meredith, Rhiannon M

AU - Hoogendijk, Witte J G

AU - Smit, August B

AU - Spijker, Sabine

N1 - Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

PY - 2017/12/20

Y1 - 2017/12/20

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1126/scitranslmed.aai8753

DO - 10.1126/scitranslmed.aai8753

M3 - Article

VL - 9

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 421

ER -