Abstract
Physical exercise improves multiple aspects of hippocampal function. In line with the notion that neuronal activity is key to promoting neuronal functions, previous literature has consistently demonstrated that acute bouts of exercise evoke neuronal activation in the hippocampus. Repeated activating stimuli lead to an accumulation of the transcription factor ΔFosB, which mediates long-term neural plasticity. In this study, we tested the hypothesis that long-term voluntary wheel running induces ΔFosB expression in the hippocampus, and examined any potential region-specific effects within the hippocampal subfields along the dorso–ventral axis. Male C57BL/6 mice were housed with or without a running wheel for 4 weeks. Long-term wheel running significantly increased FosB/ΔFosB immunoreactivity in all hippocampal regions measured (i.e., in the DG, CA1, and CA3 subfields of both the dorsal and ventral hippocampus). Results confirmed that wheel running induced region-specific expression of FosB/ΔFosB immunoreactivity in the cortex, suggesting that the uniform increase in FosB/ΔFosB within the hippocampus is not a non-specific consequence of running. Western blot data indicated that the increased hippocampal FosB/ΔFosB immunoreactivity was primarily due to increased ΔFosB. These results suggest that long-term physical exercise is a potent trigger for ΔFosB induction throughout the entire hippocampus, which would explain why exercise can improve both dorsal and ventral hippocampus-dependent functions. Interestingly, we found that FosB/ΔFosB expression in the DG was positively correlated with the number of doublecortin-immunoreactive (i.e., immature) neurons. Although the mechanisms by which ΔFosB mediates exercise-induced neurogenesis are still uncertain, these data imply that exercise-induced neurogenesis is at least activity dependent. Taken together, our current results suggest that ΔFosB is a new molecular target involved in regulating exercise-induced hippocampal plasticity.
Highlights
Exercise confers diverse benefits on molecular, structural, and functional aspects of the hippocampus in rodents [1,2], some of which were supported by human studies [3,4]
Immunohistochemical studies using c-Fos, a marker of transient neuronal activation, have demonstrated that both forced and voluntary running increased c-Fos expression in the dentate gyrus (DG), CA1, and CA3 subfields of the rodent hippocampus [5,6,7]
The correlative association between FosB/ΔFosB expression and neurogenesis was investigated as the first step in seeking the functional implications of exercise-induced ΔFosB induction in regulating hippocampal plasticity
Summary
Exercise confers diverse benefits on molecular, structural, and functional aspects of the hippocampus in rodents [1,2], some of which were supported by human studies [3,4]. Studies have demonstrated that physiological stimuli induce different patterns of c-Fos expression in the dorsal and ventral portions of the hippocampus [31,32,33] Because exercise improves both dorsal [34,35,36,37] and ventral hippocampus-dependent functions [24,25,38], it is important to examine whether long-term voluntary running causes regionspecific expression of ΔFosB in the hippocampus. The primary hypothesis of this study was that long-term voluntary wheel running would induce ΔFosB expression in the mouse hippocampus This hypothesis was investigated by FosB/ΔFosB immunohistochemistry in the dorsal and ventral hippocampal subfields, DG, CA1, and CA3, with extra emphasis on identifying region-specific induction. The correlative association between FosB/ΔFosB expression and neurogenesis was investigated as the first step in seeking the functional implications of exercise-induced ΔFosB induction in regulating hippocampal plasticity
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