Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression.
Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental an...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5598988?pdf=render |
| _version_ | 1819140539729051648 |
|---|---|
| author | Erin M van Buel Hannes Sigrist Erich Seifritz Lianne Fikse Fokko J Bosker Robert A Schoevers Hans C Klein Christopher R Pryce Ulrich Lm Eisel |
| author_facet | Erin M van Buel Hannes Sigrist Erich Seifritz Lianne Fikse Fokko J Bosker Robert A Schoevers Hans C Klein Christopher R Pryce Ulrich Lm Eisel |
| author_sort | Erin M van Buel |
| collection | DOAJ |
| description | Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects. |
| first_indexed | 2024-12-22T11:40:10Z |
| format | Article |
| id | doaj.art-7d25ece539074d9ea7d8b74a2f994b19 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T11:40:10Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7d25ece539074d9ea7d8b74a2f994b192022-12-21T18:27:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01129e018460310.1371/journal.pone.0184603Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression.Erin M van BuelHannes SigristErich SeifritzLianne FikseFokko J BoskerRobert A SchoeversHans C KleinChristopher R PryceUlrich Lm EiselElectroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects.http://europepmc.org/articles/PMC5598988?pdf=render |
| spellingShingle | Erin M van Buel Hannes Sigrist Erich Seifritz Lianne Fikse Fokko J Bosker Robert A Schoevers Hans C Klein Christopher R Pryce Ulrich Lm Eisel Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression. PLoS ONE |
| title | Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression. |
| title_full | Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression. |
| title_fullStr | Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression. |
| title_full_unstemmed | Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression. |
| title_short | Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression. |
| title_sort | mouse repeated electroconvulsive seizure ecs does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy ect side effects in the treatment of depression |
| url | http://europepmc.org/articles/PMC5598988?pdf=render |
| work_keys_str_mv | AT erinmvanbuel mouserepeatedelectroconvulsiveseizureecsdoesnotreversesocialstresseffectsbutdoesinducebehavioralandhippocampalchangesrelevanttoelectroconvulsivetherapyectsideeffectsinthetreatmentofdepression AT hannessigrist mouserepeatedelectroconvulsiveseizureecsdoesnotreversesocialstresseffectsbutdoesinducebehavioralandhippocampalchangesrelevanttoelectroconvulsivetherapyectsideeffectsinthetreatmentofdepression AT erichseifritz mouserepeatedelectroconvulsiveseizureecsdoesnotreversesocialstresseffectsbutdoesinducebehavioralandhippocampalchangesrelevanttoelectroconvulsivetherapyectsideeffectsinthetreatmentofdepression AT liannefikse mouserepeatedelectroconvulsiveseizureecsdoesnotreversesocialstresseffectsbutdoesinducebehavioralandhippocampalchangesrelevanttoelectroconvulsivetherapyectsideeffectsinthetreatmentofdepression AT fokkojbosker mouserepeatedelectroconvulsiveseizureecsdoesnotreversesocialstresseffectsbutdoesinducebehavioralandhippocampalchangesrelevanttoelectroconvulsivetherapyectsideeffectsinthetreatmentofdepression AT robertaschoevers mouserepeatedelectroconvulsiveseizureecsdoesnotreversesocialstresseffectsbutdoesinducebehavioralandhippocampalchangesrelevanttoelectroconvulsivetherapyectsideeffectsinthetreatmentofdepression AT hanscklein mouserepeatedelectroconvulsiveseizureecsdoesnotreversesocialstresseffectsbutdoesinducebehavioralandhippocampalchangesrelevanttoelectroconvulsivetherapyectsideeffectsinthetreatmentofdepression AT christopherrpryce mouserepeatedelectroconvulsiveseizureecsdoesnotreversesocialstresseffectsbutdoesinducebehavioralandhippocampalchangesrelevanttoelectroconvulsivetherapyectsideeffectsinthetreatmentofdepression AT ulrichlmeisel mouserepeatedelectroconvulsiveseizureecsdoesnotreversesocialstresseffectsbutdoesinducebehavioralandhippocampalchangesrelevanttoelectroconvulsivetherapyectsideeffectsinthetreatmentofdepression |