The role of exercise in depression: Preclinical studies in two distinct animal models
Translated title
Motions rolle i depression: Prækliniske studier af to særskilte dyremodeller
Author
Fischer, Christina Weide
Term
4. term
Publication year
2011
Submitted on
2011-06-01
Pages
88
Abstract
Depression er en alvorlig og invaliderende sygdom, som rammer omkring hver femte person i løbet af livet. Behandling er vanskelig, fordi depression viser sig forskelligt fra person til person og omfatter både psykiske, adfærdsmæssige og kropslige symptomer. Kun cirka en tredjedel får god effekt af almindelig antidepressiv medicin, så nye tilgange er nødvendige. Fysisk træning er en lovende, ikke-medicinsk strategi, der kan supplere eksisterende behandling. Vi undersøgte, om regelmæssig frivillig løbetræning kan virke antidepressivt i to rotte-modeller. Den ene var en genetisk model med Flinders Sensitive Line (FSL, en depressiv rotte-linje) og deres kontroller, Flinders Resistant Line (FRL). Den anden var en inflammationsmodel, hvor Sprague Dawley-rotter fik lipopolysakkarid (LPS) i 8 uger for at skabe langvarig betændelse. Rotterne fik enten langvarig adgang til et løbehjul i buret (et hjul, som rotter kan løbe i), medicinen imipramin (15 mg/kg/dag), eller en kombination af begge. Vi vurderede depression‑lignende adfærd med forced swim test (FST, hvor øget immobilitet ses som et depressionssignal) og angst‑lignende adfærd med elevated plus maze (EPM). I FSL-rotter målte vi desuden metaboliske markører, genaktivitet (mRNA) for udvalgte proteiner, og blodniveauer af BDNF, et vækstfaktorprotein som er vigtigt for hjernens plasticitet. I FSL/FRL-modellen var et uventet hovedfund, at enkeltvis husning (nødvendig for at måle hver rottes løbeaktivitet præcist) ændrede de sædvanlige forskelle mellem stammerne, både i FST‑adfærd og i visse metaboliske mål. Under disse betingelser gav træning ikke en klar antidepressiv effekt i FSL-rotter, muligvis fordi de løb meget lidt. Imipramin alene havde heller ingen tydelig effekt, men kombinationen af træning og imipramin reducerede depression‑lignende adfærd i FSL-rotter. Det tyder på, at træning kan forstærke virkningen af antidepressiv medicin. I LPS-modellen gav den langvarige betændelse især en vedvarende sygdomsadfærd frem for klassisk depression‑lignende adfærd. LPS øgede immobilitet i FST, og både træning og imipramin vendte denne effekt, hvilket er foreneligt med, at de modvirkede den inflammatoriske påvirkning. Sygdomsadfærden mindskede ikke rotternes løbeaktivitet, hvilket kan forklare, hvorfor træning virkede mere gavnligt her end i FSL/FRL-modellen. Samlet peger resultaterne på, at regelmæssig træning kan være et nyttigt supplement eller alternativ til antidepressiv behandling, men effekten afhænger af model og ramme (som husningsforhold og lyst til at løbe). Flere bekræftende studier er nødvendige.
Depression is a serious and disabling illness that affects about one in five people over a lifetime. Treatment is challenging because depression is highly variable and includes psychological, behavioral, and physical symptoms. Only around one‑third of patients respond well to standard antidepressant drugs, so new approaches are needed. Physical exercise is a promising non‑drug strategy that could support existing treatments. We tested whether regular voluntary running could have antidepressant effects in two rat models. One was a genetic model using Flinders Sensitive Line (FSL, a depressive rat line) and their controls, Flinders Resistant Line (FRL). The other was an inflammatory model in which Sprague Dawley rats received lipopolysaccharide (LPS) for 8 weeks to induce sustained inflammation. Rats either had long‑term access to a running wheel, received imipramine (15 mg/kg/day), or both. We assessed depression‑like behavior with the forced swim test (FST, where greater immobility is interpreted as a depression signal) and anxiety‑like behavior with the elevated plus maze (EPM). In FSL rats we also measured metabolic markers, gene activity (mRNA) for selected proteins, and blood levels of BDNF, a growth factor important for brain plasticity. In the FSL/FRL model, a key, unexpected finding was that housing rats alone (necessary to measure each animal’s running precisely) changed the usual differences between strains in FST behavior and affected some metabolic measures. Under these conditions, exercise did not show clear antidepressant‑like effects in FSL rats, possibly because they ran very little. Imipramine alone also did not help, but combining exercise with imipramine reduced depression‑like behavior in FSL rats. This suggests exercise may enhance the effects of antidepressant medication. In the LPS model, chronic inflammation produced a prolonged sickness state rather than classic depression‑like behavior. LPS increased immobility in the FST, and both exercise and imipramine reversed this effect, consistent with counteracting inflammation. Notably, sickness did not reduce running, which may explain why exercise appeared more beneficial here than in the FSL/FRL experiment. Overall, the findings indicate that regular exercise could be a useful add‑on or alternative to antidepressants, but its effects depend on the model and context (such as housing conditions and willingness to run). Further confirmatory studies are needed.
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