SPINAL-CORD GLT-1 GLUTAMATE TRANSPORTER AND BLOOD GLUTAMIC-ACID ALTERATIONS IN MOTOR-NEURON DEGENERATION (MND) MICE

This study characterizes for the first time neurochemical mechanisms i n Mnd mice, initially described as a model of motor neuron disease and more recently proposed as a model for neuronal ceroid lipofuscinosis. A selective decrease (-30%) of [H-3]glutamate uptake was found in spi nal cord but not cortical synaptosomes of Mnd mice aged 28 weeks, when they show histopathological alterations, complete blindness and moder ate neurological deficits. In spite of the widespread presence of stor ed material in neurons in many brain regions and spinal cord, the acti ve transport of [H-3]serotonin, [H-3]dopamine and depolarization-induc ed [H-3]serotonin release were not affected. Spinal EAACl glutamate tr ansporter protein was significantly decreased in some but not all aged mice by 36% on average, possibly due to the loss of motor neurons. GL T-1 immunoreactivity was reduced by 34% in 28-week-old Mnd mice, while GLAST immunoreactivity was not affected. In Mnd mice aged 14 weeks, w hen there was no apparent alteration of motor function, the defect in the glial transporter protein GLT-1 was similar to that in 28-week-old mice (25%). Blood glutamic acid concentration was increased in Mnd mi ce aged 14-22 weeks. We suggest that the early decrease of GLT-1 prote in might raise the extrasynaptic glutamic acid concentration, and cont ribute to the loss of motor neurons in affected mice, resulting in low [H-3]glutamate uptake, low EAACl immunoreactivity and neurological de ficits. (C) 1998 Elsevier Science B.V.