MOUSE MOLONEY LEUKEMIA-VIRUS INFECTS MICROGLIA BUT NOT NEURONS EVEN THOUGH IT INDUCES MOTOR-NEURON DISEASE

Motor neuron degeneration caused by ts1 MoMuLV occurs by an indirect m echanism and hypothetically appears associated with a two-cell or thre e-cell pathogenesis hypothesis. The first step in this hypothesis is a ssociated with a small subset of resident microglial cells that serve as the principal target cells for ts1 MoMuLV infection. The second ste p is likely linked to trophic events, probably mediated by cytokines, that lead to hypertrophy and activation of a substantial number of add itional microglial cells (autocrine effect) and adjacent astrocytes (p aracrine effect). The third step in this hypothesis appears related to indirect neuronal degeneration mediated by cytotoxins produced by act ivated microglial cells and astrocytes. In this last step, motor neuro ns located within these foci of activated microglial cells and astrocy tes are 'innocent bystander cells' and degenerate and die due to parac rine effects. The mechanism of motor neuron degeneration is poorly und erstood but is likely linked to a sequential cascade of trophic factor s and cytokines resulting in a final common pathway for motor neuron d eath involving production of oxidative radicals, excitatory aminoacid neurotransmitter-like substances, prostaglandins, or nitric oxide.