Ventral root avulsion leads to downregulation of GluR2 subunit in spinal motoneurons in adult rats.

It has been observed that motor neuron death is induced in adult rats by ventral root avulsion which involves pulling out the spinal cord root. Since motor neurons are reported to be selectively vulnerable to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor-mediated injury in vitro, we investigated changes in the expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate-receptor subunits in rat spinal motor neurons after ventral root avulsion. The L4-L5 ventral roots of adult Sprague-Dawley rats were avulsed by an extravertebral extraction procedure. After an appropriate survival time, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate-receptor subunits were detected immunohistochemically in the L4-L5 segments. Ventral root avulsion resulted in a 60% loss of motor neurons by 14 days after surgery. GluR2 labeling in motor neurons was markedly decreased after avulsion, but before the onset of motor neuron death, while the GluR1 and GluR4 labeling of motor neurons remained unchanged. Intrathecal administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate-receptor antagonists rescued a significant number of injured motor neurons from cell death. In contrast, N-methyl-D-aspartate-receptor antagonists did not prevent motor neuron death. Since the presence of GluR2 subunit renders heteromeric alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors Ca(2+)-impermeable, the downregulation of GluR2 may result in increased formation of GluR2-lacking, Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors in motor neurons and could contribute to motor neuron death after ventral root avulsion.