Rapid Cellular Genesis and Apoptosis: Effects of Exercise in the Adult Rat Abigail L. Kerr and Rodney A. Swain University of Wisconsin—Milwaukee Long-term aerobic exercise improves cognition in both human and nonhuman animals and induces plastic changes in the central nervous system (CNS), including neurogenesis and angiogenesis. However, the early and immediate effects of exercise on the CNS have not been adequately explored. There is some evidence to suggest that exercise is initially challenging to the nervous system and that the plastic changes commonly associated with chronic exercise may result as adaptations to this challenge. The current experiment assessed levels of apoptosis, angiogenesis, and neurogenesis during the first week of an exercise regimen in the adult rat. The results indicate that exercise rapidly induces these processes in the hippocampus and cerebellum. The temporal pattern of these events suggests that voluntary exercise in the adult rat rapidly and transiently induces apoptosis, followed by angiogenesis. Neurogenesis is an immediate and independent consequence of exercise in the hippocampus that may require the additional metabolic support supplied by angiogenesis. This is the first report of CNS neuronal apoptosis as a consequence of exercise in the adult rat and suggests that this process is a potential mediator of rapid exercise-induced plasticity. Keywords: exercise-induced plasticity, angiogenesis, neurogenesis Aerobic exercise promotes enhanced learning and memory in both human and nonhuman animals. In rodents, aerobic exercise is also associated with improved recovery following ischemic insult (Lee, Kim, Kim, et al., 2003; Lee, Kim, Lee, et al., 2003; Sim, Kim, Kim, Shin, & Kim, 2004) and improved cognitive perfor- mance on a variety of tasks including the Morris water maze (MWM), contextual fear conditioning, and radial arm maze (An- derson et al., 2000; Baruch, Swain, & Helmstetter, 2004; Fordyce & Wehner, 1993; Gobbo & O’Mara, 2004; Vaynman, Ying, & Gomez-Pinilla, 2004). In humans, exercise has been associated with improved cognitive performance in aging patients (Churchill et al., 2002; Kramer & Erickson, 2007; Kramer, Erickson, & Colcombe, 2006). Long-term exercise regimens also enhance blood perfusion and increase vascularization and neurogenesis (the development of new neurons) in nervous system structures associated with learn- ing and memory, such as the hippocampus (Kempermann, Kuhn, & Gage, 1997; Kim et al., 2002; van Praag, Shubert, Zhao, & Gage, 2005). At the cellular level, extended periods of exercise are associated with increased angiogenesis (the sprouting of new cap- illaries from preexisting blood vessels; Black, Zelanzny, & Gree- nough, 1991; Isaacs, Anderson, Alcantara, Black, & Greenough, 1992; Sikorski, Hebert, & Swain, 2008; Swain et al., 2003), neurogenesis (Kim et al., 2002; van Praag, Kempermann, & Gage, 1999; van Praag et al., 2005), or both, in various areas of the brain, including the hippocampus, motor cortex, and cerebellum. Research conducted in regard to stroke rehabilitation suggests that the beneficial effects of exercise may be somewhat compli- cated. Although several studies report beneficial outcomes of exercise programs following injury, some studies have found that exercise regimens exacerbate lesion size in animals exposed to focal ischemia (Griesbach, Gomez-Pinilla, & Hovda, 2004a). These contradictory reports suggest that there may be a sensitive window that follows lesion induction during which exercise is actually detrimental to functional recovery. Although the extent of this window has not been definitively determined, the literature suggests that it may be somewhere between zero and 48 hr post- insult (Humm, Kozlowski, James, Gotts, & Schallert, 1998; Koz- lowski, James, & Schallert, 1996; Risedal, Zeng, & Johansson, 1999). These reports suggest that exercise may initially be chal- lenging to the CNS, which is exacerbated in animals with central nervous system CNS injury, and that the neural plasticity associ- ated with exercise may be a response to this challenge. This experiment was designed to investigate the immediate and early physiological consequences of aerobic exercise. Western blot analysis revealed that aerobic activity leads to rapid and transient increases in cellular apoptosis, followed by increases in angiogen- esis in the cerebellum. In the hippocampus, neurogenesis was found to be a robust and immediate consequence of exercise that may require the additional vascular supply instigated by running. These findings reveal new information in regard to the temporal effects of early exercise-induced plasticity, which has been previ- ously unexplored in the adult rat. These findings further our understanding of exercise-induced plasticity and provide the first Abigail L. Kerr and Rodney A. Swain, Department of Psychology, University of Wisconsin—Milwaukee. Abigail L. Kerr is now at the Department of Psychology, University of Texas at Austin. The research described in this paper was supported in part by a grant to the author, Abigail Kerr, from the American Psychological Association. We thank Peter and Cathy Johnson for financial contributions to this research. For technical assistance, we thank Fred Helmstetter, Timothy Jarome, and Mary Lonergan. Correspondence concerning this article should be addressed to Rodney A. Swain, Department of Psychology, University of Wisconsin— Milwaukee, PO Box 413, Milwaukee, WI 53201. E-mail: rswain@ uwm.edu Behavioral Neuroscience © 2011 American Psychological Association 2011, Vol. 125, No. 1, 1–9 0735-7044/11/$12.00 DOI: 10.1037/a0022332 1 This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.