Altered brain metabolism in the C57BL/Wld mouse strain detected by magnetic resonance spectroscopy: association with delayed Wallerian degeneration?
In the C57BL/Wld(s) (Wld) mouse strain, both PNS and CNS axonal disintegration during Wallerian degeneration is dramatically slowed, with isolated axons being able to conduct compound action potentials (CAPs) for several weeks post-transection. The ability to conduct a CAP signifies the presence of an intact plasma membrane, normal ion gradients, and functioning ion channels. In neurons, ion homeostasis is primarily regulated by the Na(+)-K(+)-ATPase, which utilizes approximately 50% of neuronal energy output. To investigate the possibility that the Wld mutation prolongs axonal degeneration by conferring a more favorable energetic status to neurons or alters metabolism, we used 31P and 1H magnetic resonance spectroscopy (MRS) to compare the cerebral and muscle energy metabolism, membrane phospholipid contents, and water-soluble metabolites of Wld and wild-type (C57BL/6J [6J], and BALB/c) mouse strains. We first demonstrate that, with advancing age, transected Wld CNS nerves degenerate faster, paralleling previous findings in the PNS. We found significantly decreased phosphocreatine and phosphomonoester concentrations in the brains of Wld mice at 1- and 2-months of age compared to both 6J and BALB/c mice, but we failed to find differences in the adenylate (ATP, ADP, or AMP) or phospholipid concentrations. In another excitable tissue, skeletal muscle, no differences in energy-containing metabolites were detected. High resolution 1H MRS indicated that at 1 month of age, Wld brains have cytosolic levels of glutamate and phosphocholine that are significantly decreased, relative to total N-acetyl aspartate content. Our results demonstrate that delayed Wallerian degeneration in the C57BL/Wld mouse strain is associated with altered cerebral metabolism, although these changes may be secondary to the mutation.[1]References
- Altered brain metabolism in the C57BL/Wld mouse strain detected by magnetic resonance spectroscopy: association with delayed Wallerian degeneration? Tsao, J.W., Paramananthan, N., Parkes, H.G., Dunn, J.F. J. Neurol. Sci. (1999) [Pubmed]
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