ORIGINAL ARTICLE The hippocampus and exercise: histological correlates of MR-detected volume changes Sarah V. Biedermann • Johannes Fuss • Jo ¨rg Steinle • Matthias K. Auer • Christof Dormann • Claudia Falfa ´n-Melgoza • Gabriele Ende • Peter Gass • Wolfgang Weber-Fahr Received: 19 November 2014 / Accepted: 22 December 2014 Ó Springer-Verlag Berlin Heidelberg 2014 Abstract Growing evidence indicates that physical exercise increases hippocampal volume. This has consis- tently been shown in mice and men using magnetic reso- nance imaging. On the other hand, histological studies have reported profound alterations on a cellular level including increased adult hippocampal neurogenesis after exercise. A combined investigation of both phenomena has not been documented so far although a causal role of adult neuro- genesis for increased hippocampal volume has been sug- gested before. We investigated 20 voluntary wheel running and 20 sedentary mice after a period of 2 month voluntary wheel running. Half of each group received focalized hippocampal irradiation to inhibit neurogenesis prior to wheel running. Structural MRI and histological investiga- tions concerning newborn neurons (DCX), glial cells (GFAP), microglia, proliferating and pyknotic cells, neu- ronal activation, as well as blood vessel density and ar- borisation were performed. In a regression model, neurogenesis was the marker best explaining hippocampal gray matter volume. Individual analyses showed a positive correlation of gray matter volume with DCX-positive newborn neurons in the subgroups, too. GFAP-positive cells significantly interacted with gray matter volume with a positive correlation in sham-irradiated mice and no cor- relation in irradiated mice. Although neurogenesis appears to be an important marker of higher hippocampal gray matter volume, a monocausal relationship was not indi- cated, requesting further investigations. Keywords Neurogenesis Á Magnetic resonance imaging Á Voxel-based morphometry Á Exercise Á Hippocampus Á Histology Introduction Hippocampal gray matter (GM) volume decreases in adults with advancing age (Giedd et al. 1999). Some neuropsy- chiatric diseases, such as Alzheimer’s disease, as well as neurotoxic agents including alcohol aggravate this process of normal healthy aging. On the other hand, environmental factors such as exercise (Erickson et al. 2009) have tre- mendous effects on hippocampal structure and function and increase hippocampal volume. Using magnetic reso- nance imaging (MRI), the impact of aerobic exercise on S.V. Biedermann and J. Fuss share first authorship. P. Gass and W. Weber-Fahr share last authorship. S. V. Biedermann Á W. Weber-Fahr Departments of Neuroimaging and Psychiatry and Psychotherapy, Medical Faculty Mannheim, Central Institute of Mental Health Mannheim (ZI), RG Translational Imaging, University of Heidelberg, Mannheim, Germany S. V. Biedermann Á C. Falfa ´n-Melgoza Á G. Ende Á W. Weber-Fahr Department of Neuroimaging, Medical Faculty Mannheim, Central Institute of Mental Health Mannheim (ZI), University of Heidelberg, Mannheim, Germany J. Fuss (&) Á J. Steinle Á M. K. Auer Á C. Dormann Á P. Gass Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, Central Institute of Mental Health Mannheim (ZI), RG Animal Models in Psychiatry, University of Heidelberg, J 5, 68159 Mannheim, Germany e-mail: jo.fuss@uke.de M. K. Auer Department of Endocrinology, Max Planck Institute of Psychiatry, Munich, Germany 123 Brain Struct Funct DOI 10.1007/s00429-014-0976-5