In vivo voxel based morphometry: detection of increased hippocampal volume and decreased glutamate levels in exercising mice.

Voluntary exercise has tremendous effects on adult hippocampal plasticity and metabolism and thus sculpts the hippocampal structure of mammals. High-field (1)H magnetic resonance (MR) investigations at 9.4 T of metabolic and structural changes can be performed non-invasively in the living rodent brain. Numerous molecular and cellular mechanisms mediating the effects of exercise on brain plasticity and behavior have been detected in vitro. However, in vivo attempts have been rare. In this work a method for voxel based morphometry (VBM) was developed with automatic tissue segmentation in mice using a 9.4 T animal scanner equipped with a (1)H-cryogenic coil. The thus increased signal to noise ratio enabled the acquisition of high resolution T2-weighted images of the mouse brain in vivo and the creation of group specific tissue class maps for the segmentation and normalization with SPM. The method was used together with hippocampal single voxel (1)H MR spectroscopy to assess the structural and metabolic differences in the mouse brain due to voluntary wheel running. A specific increase of hippocampal volume with a concomitant decrease of hippocampal glutamate levels in voluntary running mice was observed. An inverse correlation of hippocampal gray matter volume and glutamate concentration indicates a possible implication of the glutamatergic system for hippocampal volume.