Stoica G, Barker R, Wu G, Lynn W S, Wong P K
Texas A and M University, Department of Veterinary Pathobiology, College Station 77843-4467, USA.
In Vivo. 1998 Jul-Aug;12(4):395-401.
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.
莫洛尼鼠白血病病毒（MoMuLV-ts1）的温度敏感突变体可在高度易感的新生FVB/N品系小鼠中诱发脑脊髓灰质炎和后肢麻痹。这种疾病的特征是中枢神经系统（CNS）特定靶区域内运动神经元进行性丧失和严重的胶质细胞增生。这种神经退行性变的机制尚不清楚。在中枢神经系统的新生儿感染中，据报道MoMuLV-ts1病毒在内皮细胞、室管膜细胞、星形胶质细胞和小胶质细胞内复制。由于在退化的神经元中未发现病毒或病毒产物，推测一种间接机制导致了新生感染小鼠中神经元的丧失。本研究旨在探讨兴奋性氨基酸（EAA）如谷氨酸和其他非神经递质氨基酸（NAA）在该动物模型中可能的致病作用。通过荧光高效液相色谱法分析游离氨基酸浓度。与未感染的对照小鼠相比，MoMuLV-ts1感染小鼠脑干和脊髓中游离氨基酸浓度、谷氨酸、谷氨酰胺和精氨酸的时间测量值显著降低。在感染过程中，EAA的浓度表明谷氨酸及其前体谷氨酰胺在早期感染（感染后10天-dpi）时急剧下降。这种缺乏在脊髓中持续存在（20和30 dpi），脊髓中神经元丧失最为严重，但在脑干中则不然。氨基酸精氨酸也出现类似模式。这些观察结果表明，发育中小鼠中枢神经系统中星形胶质细胞诱导的谷氨酸和精氨酸代谢紊乱，可能部分导致了该模型中观察到的运动神经元丧失。
