Effects of chronic treadmill running on neurogenesis in the dentate gyrus of the hippocampus of adult rat. Brain Res

Department of Sport and Exercise Sciences, Graduate School of Sport Sciences, Osaka University of Health and Sport Sciences, Asashirodai1-1, Kumatori-cho, Sennan-gun, Osaka 590-0496, Japan.
Brain Research (Impact Factor: 2.83). 09/2006; 1104(1):64-72. DOI: 10.1016/j.brainres.2006.05.066
Source: PubMed

ABSTRACT Proliferating astrocytes and proliferating neuroblasts have been observed in the subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus of adult rats under normal conditions. However, whether these proliferating cells are stimulated by running has not been determined. Using immunohistochemical techniques, we examined the effects of chronic treadmill running on proliferating astrocytes (PCNA+/GFAP+ cells), proliferating neuroblasts (PCNA+/DCX+ cells) and newly generated postmitotic neurons (DCX+/NeuN+ cells) in the DG of the hippocampus of adult rats and also characterized the morphological features of PCNA+/GFAP+ cells and PCNA+/DCX+ cells. PCNA+/GFAP+ cells with few processes and PCNA+/DCX+ cells without long processes were detected in the SGZ, and we determined that these are morphological features of the astrocytes and neuroblasts with proliferative ability. Chronic treadmill running (at a speed of 22 m/min, 30 min/days for 7 days) significantly increased the numbers of PCNA+/GFAP+ cells and DCX+/NeuN+ cells, and the number of PCNA+/DCX+ cells tended to increase by chronic treadmill running. These results indicate that chronic treadmill running stimulates the proliferation of astrocytes in the SGZ. Furthermore, the present study indicates that chronic treadmill running increases DCX+/NeuN+ cells that are detected in a transient stage during the neuronal maturation process. These events may be the cellular basis mediating both running-induced increases of new neurons in the DG of the hippocampus and running-induced improvement of learning and memory functions of adult rats.

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    • "In this context, Huang et al. (2013) suggested that exercise-induced cognitive improvement of middle-aged rats might be associated with an increase on the capillaries density in the rat cortex. The exercise-induced astrogliosis here observed in the sham group is supported by previous studies which demonstrated an increase in astrocytic activation and proliferation of GFAP positive cells, in the subgranular zone of the hippocampus, in healthy exercised rats (Uda et al., 2006; Li et al., 2005; Saur et al., 2014). Besides, our findings are in accordance with Valentim et al. (1999) that observed an early and late increase in both immunocontent and GFAP phosphorylation rate in the hippocampus from ischemic rats, Fig. 3 "
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    ABSTRACT: Persistent effects of pre- and postischemic exercise on glial cells activation after global cerebral ischemia remains poorly understood. Here, we investigated the effect of both pre and postischemic treadmill exercise protocols (20 min/day during 2 weeks) on glial cells immunostaining in the hippocampus of Wistar rats submitted to global ischemia. A synergistic effect between ischemia and postischemic exercise on the astrocytic area was demonstrated. Postischemic exercise partially reversed the ischemia-induced increase on the area occupied by microglia, without any effect of pre-ischemic protocol. In conclusion, postischemic exercise distinctly modulates astrocyte and microglia immunostaining in the hippocampal dentate gyrus following global cerebral ischemia in Wistar rats.
    Brain Research 10/2014; 1587. DOI:10.1016/j.brainres.2014.08.068 · 2.83 Impact Factor
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    • "For instance, Kim et al. (2003), in a study that evaluated the impact of different exercise protocols on cell proliferation , found that they may have markedly different effects on neuronal function. The mechanisms through which exercise facilitates spatial memory are still unclear, but it is believed that certain factors may be involved, such as the production of BDNF (Griffin et al., 2009; Ferreira et al., 2011), potentiation of glutamatergic transmission (O'Callaghan et al., 2007; Liu et al., 2011) and neurogenesis (Uda et al., 2006). Regarding the endocannabinoid system, our study shows that the exercise-induced spatial memory improvement was prevented by simultaneous blockade of the CB 1 receptor with AM251. "
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    ABSTRACT: It is well known that physical exercise has positive effects on cognitive functions and hippocampal plasticity. However, the underlying mechanisms have remained to be further investigated. Here we investigated the hypothesis that the memory-enhancement promoted by physical exercise relies on facilitation of the endocannabinoid system. We observed that the spatial memory tested in the object location paradigm did not persist in sedentary mice, but could be improved by 1 week of treadmill running. In addition, exercise up-regulated CB1 receptor and BDNF expression in the hippocampus. To verify if these changes required CB1 activation, we treated the mice with the selective antagonist, AM251, before each period of physical activity. In line with our hypothesis, this drug prevented the exercise-induced memory enhancement and BDNF expression. Furthermore, AM251 reduced CB1 expression. To test if facilitating the endocannabinoid system signaling would mimic the alterations observed after exercise, we treated sedentary animals during 1 week with the anandamide-hydrolysis inhibitor, URB597. Mice treated with this drug recognized the object in a new location and have increased levels of CB1 and BDNF expression in the hippocampus, showing that potentiating the endocanabinoid system equally benefits memory. In conclusion, the favorable effects of exercise upon spatial memory and BDNF expression depend on facilitation of CB1 receptor signaling, which can be mimic by inhibition of anandamide hydrolysis in sedentary animals. Our results suggest that, at least in part, the promnesic effect of the exercise is dependent of CB1 receptor activation and is mediated by BDNF. © 2013 Wiley Periodicals, Inc.
    Hippocampus 01/2014; 24(1). DOI:10.1002/hipo.22206 · 4.30 Impact Factor
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    • "Furthermore, it has been theorized that forced exercise is a better model for humans, as it is performed for a restricted period of time, and forced running also models most humans' attitude toward exercise; whereas voluntary exercise would more accurately model athletic individuals that would choose to engage in prolonged physical activity (i.e. endurance athletes) [24] [25]. In light of this, forced daily exercise is a better model for studying the effects of exercise in recovering addicted subjects who are being encouraged to run as part of the activities of a substance abuse treatment program. "
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    ABSTRACT: Exercise affects neuroplasticity and neurotransmission including dopamine (DA), which modulates drug-taking behavior. Previous research in rodents has shown that exercise may attenuate the rewarding effects of drugs of abuse. The present study examined the effects of high and low exercise on cocaine responses in male Wistar rats that had been trained to self-administer and were compared to a group of sedentary rats. High exercise rats (HE) ran daily on a treadmill for 2hours and low exercise (LE) ran daily for one hour. After 6 weeks of this exercise regimen, rats were tested over 2 days for reinstatement (day 1: cue-induced reinstatement; day 2: cocaine-primed reinstatement). During cue-induced reinstatement, the sedentary rats showed the expected increase in active lever responses when compared to maintenance, whereas these increased responses were inhibited in the exercised rats (HE and LE). During cocaine-primed reinstatement, however, there was a significant increase in active lever presses when compared to maintenance only in the HE group. This data suggests that chronic exercise during abstinence attenuates the cue-induced reinstatement seen in the sedentary rats by 26% (LE) and 21% (HE). In contrast, only the high exercise rats exhibited sensitized cocaine-seeking behavior (active lever presses) following cocaine-primed reinstatement. Finally, while sedentary rats increased locomotor activity during cocaine-primed reinstatement over that seen with cocaine during maintenance, this was not observed in the exercised rats, suggesting that exercise may interfere with the sensitized locomotor response during cocaine reinstatement.
    Behavioural brain research 10/2012; 239(1). DOI:10.1016/j.bbr.2012.10.035 · 3.39 Impact Factor
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