Quantitative variation of free amino acids in the central nervous system of MoMuLV-ts1-infected mice.
A temperature-sensitive mutant of Moloney murine leukemia virus (MoMuLV-ts1) induces polioencephalomyelopathy and hind limb paralysis in highly susceptible FVB/N strains of neonatal mice. This disease is characterized by progressive motor neurons loss and severe gliosis within specific target areas of the central nervous system (CNS). The mechanism(s) of this neurodegeneration is unknown. In the neonatal infection of the CNS, the MoMuLV-ts1 virus was reported to replicate within the endothelial, ependymal, astrocytes and microglial cells. Since no virus or viral products were recognized in the degenerating neurons, it is postulated that an indirect mechanism(s) caused the loss of neurons in the neonatally infected mice. This study was undertaken to investigate the possible pathogenic role of excitatory amino acids (EAAs) such as glutamate and other nonneurotransmitters amino acids (NAAs) in this animal model. The free amino acids concentration was analysed by a fluorometric HPLC method. The temporal measurements of the free amino acids concentration, glutamate, glutamine and arginine from the brain stem and spinal cord of MoMuLV-ts1-infected mice was significantly decreased when compared with the control non-infected mice. The concentration of EAAs during the course of this infection indicated a sharp decline in glutamate and its precursor, glutamine with early infection (10 days post infection-dpi). This deficiency persisted (20 and 30 dpi) in the spinal cord, where the neuronal loss was most severe, but not in the brain stem. A similar pattern occurs with the amino acid arginine. These observations suggest that an astrocyte-induced metabolic disturbance of glutamate and arginine in the CNS of developing mice, could be, in part responsible for the loss of motor neurons observed in this model.
Stoica
G
G
Texas A and M University, Department of Veterinary Pathobiology, College Station 77843-4467, USA.
Barker
R
R
Wu
G
G
Lynn
W S
WS
Wong
P K
PK
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001933:Brain Stem / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism*; D005260:Female; D051379:Mice; D008979:Moloney murine leukemia virus; D012192:Retroviridae Infections / Q000378:metabolism* / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism; D014412:Tumor Virus Infections / Q000378:metabolism* / Q000473:pathology
D000596:Amino Acids