Exercise Maintains Dendritic Complexity in an Animal Model of Posttraumatic Stress Disorder JAY R. HOFFMAN 1 , HADAS COHEN 2 , ISHAY OSTFELD 3 , ZEEV KAPLAN 2 , JOSEPH ZOHAR 4 , and HAGIT COHEN 2 1 Institute of Exercise Physiology and Wellness, Sport and Exercise Science, Burnett School of Biomedical Science, University of Central Florida, Orlando, FL; 2 Anxiety and Stress Research Unit, Faculty of Health Sciences, Division of Psychiatry, Beer-Sheva Mental Health Center, Ben-Gurion University of the Negev, Beer-Sheva, ISRAEL; 3 Israel Defense Force, Medical Corps, Tel Hashomer, ISRAEL; and 4 Division of Psychiatry, The State of Israel Ministry of Health, The Chaim Sheba Medical Center, Ramat-Gan, Israel, Sackler Medical School, Tel-Aviv University, Tel-Aviv, ISRAEL ABSTRACT HOFFMAN, J. R., H. COHEN, I. OSTFELD, Z. KAPLAN, J. ZOHAR, and H. COHEN. Exercise Maintains Dendritic Complexity in an Animal Model of Posttraumatic Stress Disorder. Med. Sci. Sports Exerc., Vol. 48, No. 12, pp. 2487–2494, 2016. Introduction: This study examined the effect of endurance exercise on dendritic arborization in the dentate gyrus subregion in rodents exposed to a predator scent stress (PSS). Methods: Sprague–Dawley rats were randomly assigned to one of four treatment groups. In two of the groups, rats were unexposed to PSS but either remained sedentary (SED + UNEXP) or were exercised (EX + UNEXP). In the other two groups, rats were exposed to the PSS but either remained sedentary (SED + PSS) or were exercised (EX + PSS). After 6 wk of either exercise or sedentary lifestyle, rats were exposed to either the PSS or a sham protocol. During exercise, the animals ran on a treadmill at 15 mImin j1 , 5 minId j1 gradually increasing to 20 minId j1 ,5dIwk j1 for 6 wk. Eight days after exposure to either PSS or sham protocol, changes in the cytoarchitecture (dendritic number, dendritic length, and dendrite spine density) of the dentate gyrus subregion of the hippocampus were assessed. Results: No differences (P = 0.493) were noted in dendritic number between the groups. However, dendritic length and dendrite spine density for SED + PSS was significantly smaller (P G 0.001) than that observed in all other groups. In addition, neurons from animals in SED + PSS had significantly fewer (P G 0.001) dendritic intersections than all other groups. Conclusion: The results of this study indicate that 6 wk of endurance training can protect dendritic length and complexity, suggesting a degree of resiliency to stress. This provides further evidence for supporting the inclusion of an exercise regimen for reducing the risk of posttraumatic stress disorder. Key Words: POSTTRAUMATIC STRESS DISORDER, TRAINING, HIPPOCAMPUS, PHYSICAL ACTIVITY, BRAIN I t is well accepted that the brain displays persistent plasticity throughout life (16). Changes in the morphol- ogy of the brain appear to be dependent on the stimulus presented, which can modify behavior, learning, and re- sponse to a specific cue. Previous research has demonstrated that physical exercise is a potent stimulator for increasing the expression of neurotrophins within the hippocampus (2,11,15,17,27,28). For instance, both brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY) suggested to promote and support neuronal health in the hippocampus (2,4,28). The increase in the expression of BDNF after endurance training is reported to stimulate an increase in dendritic spine density and dendritic arborization (7,23,25). These adaptations to neuron morphology have been associated with positive changes in memory and learning (1,6). In contrast to the positive adaptations associated with exercise and brain health, stress may result in negative adap- tations in neuronal morphology. Stress induced by 5 d of sleep disturbance in rats was associated with significant reductions in dendritic spine density in both cortical and hippocampal pyramidal neurons (3). Other investigators exposed rats to 4 wk of chronic unpredictable stress (various stimuli that in- cluded daily exposure to either cold water, vibration, restraint, overcrowding, or hot air stream) and reported significant atrophy of CA3 and CA1 apical dendrites in the dorsal hippocampus (21). These changes were also associated with cognitive deficits and increased anxiety-like behavior. The effect of stress also appears to affect certain regions of the brain differently. In an examination of a rats/rodent model of posttraumatic stress disorder (PTSD), Cohen et al. (4) observed that changes in the morphology of the hippocampus and amyg- dala subregions were related to the pattern of behavioral Address for correspondence: Jay R. Hoffman, Ph.D., Institute of Exercise Physiology and Wellness, Sport and Exercise Science, Burnett School Bio- medical Science, University of Central Florida Orlando, FL 32816; E-mail: jay.hoffman@ucf.edu. Submitted for publication February 2016. Accepted for publication June 2016. 0195-9131/16/4812-2487/0 MEDICINE & SCIENCE IN SPORTS & EXERCISE Ò Copyright Ó 2016 by the American College of Sports Medicine DOI: 10.1249/MSS.0000000000001038 2487 APPLIED SCIENCES Copyright © 2016 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.