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 disintegrat ion during Wallerian degeneration is dramatically slowed, with isolated axo ns being able to conduct compound action potentials (CAPs) for several week s post-transection. The ability to conduct a CAP signifies the presence of an intact plasma membrane, normal ion gradients, and functioning ion channe ls. In neurons, ion homeostasis is primarily regulated by the Na+-K+-ATPase , which utilizes approximately 50% of neuronal energy output. To investigat e the possibility that the Wld mutation prolongs axonal degeneration by con ferring a more favorable energetic status to neurons or alters metabolism, we used P-31 and H-1 magnetic resonance spectroscopy (MRS) to compare the c erebral and muscle energy metabolism, membrane phospholipid contents, and w ater-soluble metabolites of Wld and wild-type (C57BL/6J [6J], and BALB/c) m ouse strains. We first demonstrate that, with advancing age, transected Wld CNS nerves degenerate faster, parallelling previous findings in the PNS. W e found significantly decreased phosphocreatine and phosphomonoester concen trations in the brains of Wld mice at 1- and 2-months of age compared to bo th 6J and BALB/c mice, but we failed to find differences in the adenylate ( ATP, ADP, or AMP) or phospholipid concentrations, in another excitable tiss ue, skeletal muscle, no differences in energy-containing metabolites were d etected. High resolution H-1 MRS indicated that at 1 month of age, Wld brai ns have cytosolic levels of glutamate and phosphocholine that are significa ntly decreased, relative to total N-acetyl aspartate content. Our results d emonstrate that delayed Wallerian degeneration in the C57BL/Wld mouse strai n is associated with altered cerebral metabolism, although these changes ma y be secondary to the mutation. (C) 1999 Elsevier Science B.V. All rights r eserved.