Cerebral metabolism in brains of rats infected with neuropathogenic murine leukemia viruses.

Friend murine leukemia virus A8 and PVC211 cause spongiform neurodegeneration in rat brains. Glutamate is an important neurotransmitter synthesized from alpha-ketoglutaric acid, an intermediate product of the citric acid cycle, and glutamine is synthesized from glutamate. To examine the brain metabolism of rats infected with neuropathogenic viruses, the amount of glutamate and glutamine in the brains of rats infected with A8, PVC211, and non-neuropathogenic 57 was measured using high performance liquid chromatography, and the (13)C-label incorporation into the C4 position of glutamate and glutamine from [1-(13)C] glucose was measured with (13)C nuclear magnetic resonance. In the cerebral hemisphere and region containing the brain stem and basal ganglia of rats infected with A8 and PVC211 at 8-9 weeks post-infection (wpi), the amount of glutamine was decreased compared with the 57-infected rats. The amount of glutamate was decreased in the cerebral hemisphere of the A8-infected rats and the region containing the brain stem and basal ganglia of PVC211-infected rats at 8-9 wpi. The amount of [4-(13)C] glutamine and [4-(13)C] glutamate in the cerebral hemisphere and region containing the brain stem and basal ganglia of rats infected with A8 and PVC211 at 8-9 wpi was equivalent to that of the 57-infected rats. These results suggest that in the brains of rats infected with neuropathogenic viruses, de novo synthesis of glutamate and glutamine is not decreased, but the ability to maintain quantitative levels of glutamate and glutamine is decreased compared with the brains of rats infected with non-neuropathogenic virus.