The antidepressant effect of running is associated with increased hippocampal cell proliferation

Abstract

A common trait of antidepressant drugs, electroconvulsive treatment and physical exercise is that they relieve depression and up-regulate neurotrophic factors as well as cell proliferation and neurogenesis in the hippocampus. In order to identify possible biological underpinnings of depression and the antidepressant effect of running, we analysed cell proliferation, the level of the neurotrophic factor BDNF in hippocampus and dynorphin in striatum/accumbens in 'depressed' Flinders Sensitive Line rats (FSL) and Flinders Resistant Line (FRL) rats with and without access to running-wheels. The FRL strain exhibited a higher daily running activity than the FSL strain. Wheel-running had an antidepressant effect in the 'depressed' FSL rats, as indicated by the forced swim test. In the hippocampus, cell proliferation was lower in the 'depressed' rats compared to the control FRL rats but there was no difference in BDNF or dynorphin levels in striatum/accumbens. After 5 wk of running, cell proliferation increased in FSL but not in FRL rats. BDNF and dynorphin mRNA levels were increased in FRL but not to the same extent in the in FSL rats; thus, increased BDNF and dynorphin levels were correlated to the running activity but not to the antidepressant effect of running. The only parameter that was associated to basal level of 'depression' and to the antidepressant effect was cell proliferation in the hippocampus. Thus, suppression of cell proliferation in the hippocampus could constitute one of the mechanisms that underlie depression, and physical activity might be an efficient antidepressant.

Running has Differential Effects on NPY, Opiates, and Cell Proliferation in an Animal Model of Depression and Controls

“…After 5 weeks, the distances covered were approximately 3 and 7 km/day by the FSL and FRL rats, respectively. Running during 30 days had an antidepressant-like effect as tested in the PST and also increased cell proliferation in the FSL but not in the FRL rats (Bj rnebekk et al, 2005). In contrast, running increased BDNF levels in the FRL but had no effect in the FSL rats.…”

“…Animals had access to food and water ad libitum and were subjected to a controlled 12-h light : 12-h dark-schedule (lights on at 0700). After 30 days of running, animals were analyzed in a modified version of Porsolt's swim test (see Bj rnebekk et al, 2005).…”

“…To evaluate cell proliferation, four injections of BrdU (75 mg/kg, i.p., Sigma) with 2 h intervals were administered 4 days after the swim test (Bj rnebekk et al, 2005). One FSL runner and one FSL control died after BrdU injections leaving seven FSL runners and seven FSL controls for histological analysis.…”

“…The FSL strain shows good face and predictive validity as a model of depression and in assessment of antidepressant treatments (Overstreet, 1993(Overstreet, , 1995. Recently, we found that the antidepressant effect of exercise in FSL was associated with increased hippocampal cell proliferation (Bj rnebekk et al, 2005). Thus, increased cell proliferation and neurogenesis in the SGZ appear to be one common feature of antidepressant treatments, including running.…”

“…Exercise promotes physical health and is also an efficient antidepressant in depressed patients (Blumenthal et al, 1999;Martinsen et al, 1985;Strawbridge et al, 2002) as well as in an animal model of depression (Bj rnebekk et al, 2005). In fact, in a recent follow-up study, continued exercise was more efficient in preventing depressive relapses than antidepressant medication (Babyak et al, 2000).…”