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Quantitative variation of free amino acids in the central nervous system of MoMuLV-ts1-infected mice
1Texas A and M University, Department of Veterinary Pathobiology, College Station 77843-4467, USA.
Abstract:
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.
Insights
Moloney murine leukemia virus (MoMuLV-ts1) causes motor neuron loss in mice. This study found decreased glutamate and arginine levels in infected mouse brains, suggesting astrocyte-related metabolic disturbances contribute to neurodegeneration.
Area of Science:
- Neuroscience
- Virology
- Biochemistry
Background:
- Moloney murine leukemia virus (MoMuLV-ts1) infection in neonatal mice causes polioencephalomyelopathy and motor neuron loss.
- The exact mechanism of neurodegeneration in this MoMuLV-ts1 model is not fully understood.
- Previous studies indicate MoMuLV-ts1 replicates in various CNS cells but not directly in degenerating neurons, suggesting indirect pathogenic mechanisms.
Purpose of the Study:
- To investigate the potential role of excitatory amino acids (EAAs) and other amino acids in MoMuLV-ts1-induced neurodegeneration.
- To analyze the concentration of free amino acids, specifically glutamate and non-neurotransmitter amino acids (NAAs), in the central nervous system (CNS) of infected mice.
Main Methods:
- Utilized a temperature-sensitive mutant of Moloney murine leukemia virus (MoMuLV-ts1) in susceptible FVB/N neonatal mice.
- Analyzed free amino acid concentrations, including glutamate, glutamine, and arginine, using a fluorometric High-Performance Liquid Chromatography (HPLC) method.
- Performed temporal measurements at 10, 20, and 30 days post-infection (dpi) in the brain stem and spinal cord.
Main Results:
- Significantly decreased concentrations of glutamate, glutamine, and arginine were observed in the brain stem and spinal cord of MoMuLV-ts1-infected mice compared to controls.
- A sharp decline in glutamate and its precursor, glutamine, occurred early in infection (10 dpi) and persisted in the spinal cord.
- Arginine levels followed a similar pattern, with deficiencies noted in the spinal cord where neuronal loss was most severe.
Conclusions:
- Astrocyte-induced metabolic disturbances affecting glutamate and arginine may contribute to motor neuron loss in MoMuLV-ts1-infected developing mice.
- The findings suggest indirect mechanisms, possibly involving altered amino acid metabolism, are responsible for the observed neurodegeneration.
- This study highlights the importance of amino acid homeostasis in the developing CNS and its susceptibility to viral-induced metabolic disruption.
