Long-Term Exercise Is a Potent Trigger for ΔFosB Induction in the Hippocampus along the dorso–ventral Axis

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.

Long-Term Mild, rather than Intense, Exercise Enhances Adult Hippocampal Neurogenesis and Greatly Changes the Transcriptomic Profile of the Hippocampus

“…Exercise increases adult hippocampal neurogenesis (AHN) [ 1 , 10 – 12 ], that is a continuous production of new neurons in the hippocampal dentate gyrus (DG) [ 13 – 15 ], and furthermore, exercise-enhanced AHN is considered an important cellular substrate for the development of hippocampal function [ 1 , 4 , 10 ]. The origin of AHN is adult neural stem cells, which can grow into functionally matured neurons through a development process that is divided into three main stages (cell proliferation, differentiation and functional maturity) over four to six weeks [ 13 – 15 ].…”

A atividade física voluntária e seus efeitos sobre a neurogênese hipocampal em roedores adultos – Uma revisão de literatura

“…Das publicações restantes foram encontrados estudos de oito países, sendo que Estados Unidos [22][23][24][25][26][27][28][29][30][31][32] e Alemanha [33][34][35][36][37] concentraram o maior número de publicações. Ainda, Japão 38 22,23,24,25,26,27,28,29,32,38,39,40,42,43,37 . Além dele, alguns artigos também se utilizaram de técnicas de histologia 33,34 , imunoflorescência 42,26,43,29,31 e autorradiografia 32 .…”

Cage-induced stereotypic behaviour in laboratory mice covaries with nucleus accumbens FosB/ΔFosB expression

“…However, we cannot assume this type of causality from mere correlation. Indeed, caution is urged by the way that NAc FosB elevates in response to motivationally salient stimuli, both stressors and rewards [14][15][16]25]): findings that suggest two alternative explanations for our results. One is that NAc ∆FosB and SB are independently increased by stress, with no causal connection between them; thus high SB mice find their cages particularly stressful (which elevates ∆FosB), and are highly motivated to escape (escape-attempts developing into SB: [4]).…”

“…Fos family proteins are transcription factors that regulate gene expression, ∆FosB being a highly stable FosB variant that accumulates over time with repeated stimulation, and that mediates long-term neuronal plasticity [e.g. 14,15,16]. ∆FosB thus reflects long-term neuronal activation, in a manner perhaps likely to covary with CO [7].…”