Brooks B R, Feussner G K, Lust W D
Brain Res Bull. 1983 Dec;11(6):681-6. doi: 10.1016/0361-9230(83)90011-4.
Decreased cerebrospinal fluid concentrations of cyclic nucleotides in human motor neuron disease and decreased spinal cord concentrations of cyclic nucleotides in murine (Wobbler) motor neuron disease suggest that an abnormality in cyclic nucleotide metabolism may play a role in motor neuron degeneration. Retroviruses cause decreased cellular levels of cyclic nucleotides in infected cells. We induced a motor neuron degeneration with a neurotropic retrovirus, but not with a non-neurotropic retrovirus. In paralyzed mice, mean cAMP was decreased 21% in posterior horn segments and 34% in anterior horn segments compared to controls. The proportion of spinal cord phosphorylase a decreased 24% in paralyzed mice compared to controls. The content of cGMP decreased 48% in the cerebellum and 25% in both anterior and posterior horn segments of the spinal cords of paralyzed mice compared to controls. White matter content of these chemicals did not decrease in the posterior column of affected animals. Spinal cord content of ATP increased 20-22% in all three compartments, but the spinal cord content of phosphocreatine increased dramatically in white matter (46%), posterior horn gray matter (69%), and anterior horn gray matter (103%) compared to controls. Changes in high-energy phosphate intermediate and cyclic nucleotide metabolites occurred only in topographical regions showing neuronal and astrocyte pathological changes, but did not occur in the cerebral cortex.
人类运动神经元疾病中脑脊液环核苷酸浓度降低，以及鼠类（震颤麻痹）运动神经元疾病中脊髓环核苷酸浓度降低，这表明环核苷酸代谢异常可能在运动神经元变性中起作用。逆转录病毒会导致受感染细胞中环核苷酸的细胞水平降低。我们用嗜神经逆转录病毒诱导了运动神经元变性，但非嗜神经逆转录病毒则不会。与对照组相比，瘫痪小鼠后角节段的平均环磷酸腺苷（cAMP）降低了21%，前角节段降低了34%。与对照组相比，瘫痪小鼠脊髓磷酸化酶a的比例降低了24%。与对照组相比，瘫痪小鼠小脑中环鸟苷酸（cGMP）含量降低了48%，脊髓前角和后角节段均降低了25%。在患病动物的后柱中，这些化学物质的白质含量并未降低。与对照组相比，脊髓中所有三个区域的三磷酸腺苷（ATP）含量均增加了20 - 22%，但脊髓中磷酸肌酸的含量在白质（46%）、后角灰质（69%）和前角灰质（103%）中显著增加。高能磷酸中间体和环核苷酸代谢物的变化仅发生在显示神经元和星形胶质细胞病理变化的地形区域，而在大脑皮层中未发生。
