Cerebral Metabolism in Brains of Rats Infected with Neuropathogenic Murine Leukemia Viruses

Abstract

ABSTRACT. Friend murine leukemia virus A8 and PVC211 cause spongiform neurodegeneration in rat brains. Glutamate is an important neurotransmitter synthesized from α-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. KEY WORDS: cerebral metabolism, 13 C, mouse retrovirus, neuropathogenicity.J. Vet. Med. Sci. 68(3): 259-265, 2006 Murine leukemia viruses (MLVs) cause neurodegenerative diseases without inflammatory infiltrates. The first case that showed that murine retroviruses could induce neurological disorders was found in wild mice, which developed hind limb paralysis accompanied with replication-competent ecotropic MLVs, from the Lake Casitas region of California [9,16]. Ecotropic CasBrE MLV isolated from these mice caused a similar disease in the central nervous system (CNS) in laboratory mice [7]. Since the discovery of CasBrE MLV 20 years ago, other neuropathogenic murine retroviruses have been found. , cause neurodegenerative disease in mice and/or rats. The neuropathology of these viruses is characterized by spongiform neurodegeneration without inflammatory infiltrates, primarily involving the motor system of the brain and spinal cord, and is associated with widespread astrogliosis and neuropil vacuolation [1,3,17,24]. One common feature of these viruses, including A8 and PVC211, is that the primary determinant for induction of neurodegenerative disease is the env gene, although other viral genes also have an effect on neuropathogenicity [5,6,15,20,21,26,28]. Some uninfected neurons may exhibit cytopathogenicity, indicating an indirect mechanism of MLV-induced neuropathogenicity [8,19]. However, the patho...

A simple convenient synthesis ofl-[4-13C]glutamine

“…Glutamine is then sent from astrocytes to neurons, converted into glutamate again, and used for neurotransmission. 3 This neuron-astrocyte/glutamate-glutamine cycle is usually studied by using 13 C-labeled glucose [4][5][6][7][8] or uniform-13 C-labeled glutamic acid and glutamine. [9][10][11] For detailed in vivo nuclear magnetic resonance (NMR) study of this cycle, for example, to confirm that glutamine is used as an energy source in neurons, single-13 C-labeled L-glutamine (1) is required.…”