Regional metabolic differences in rat prefrontal cortex measured with in vivo 1 H-MRS correlate with regional histochemical differences.

Abstract

Many neurological/psychiatric disorders are associated with metabolic abnormalities in the brain observable with in vivo proton MRS (1 H-MRS). The underlying molecular/cellular mechanisms and functional correlations of such metabolic alterations, however, are yet to be understood fully. The rodent prefrontal cortex (PFC) is comprised of multiple sub-regions with distinctive cytoarchitecture and functions, providing a good model system to study the correlations among cerebral metabolism, regional cytoarchitecture and connectivity. In this study, the metabolic profiles in two voxels containing mainly the medial PFC (mPFC) and posterior part of the cingulate cortex (pCG), respectively, were measured with single-voxel in vivo 1 H-MRS in adult male rats. The levels of glutamine synthetase and glutamatergic synaptic proteins, including vesicular glutamate transporter 1, vesicular glutamate transporter 2 (VGLUT2) and post-synaptic density protein 95 (PSD95), as well as the density of astrocytes, in these two regions were also compared semi-quantitatively. It was shown that, relative to the pCG voxel, the mPFC voxel had significantly higher N-acetyl aspartate, glutamate (Glu), glutamine (Gln), Glx (Glu+Gln), myo-inositol and taurine levels. The VGLUT2/PSD95 levels and astrocyte density were also higher in the mPFC voxel than in the pCG voxel. Taken together, these results indicated that regional metabolic variations in the PFC of the adult male rat may reflect regional differences in the density of astrocytes and glutamatergic terminals associated with subcortical projections. The study provided a link between the Glu concentration measured with localized in vivo 1 H-MRS and regional glutamatergic activities/connections in the rat PFC.