Expression of AMPA and NMDA receptor subunits in the cervical spinal cord of wobbler mice

No differences were found in the distribution of AMPA and NMDA receptor subunits at both ages. Western blots analysis showed a trend of reduction in AMPA and NMDA receptor subunits, mainly GluR1 and NR2A, exclusively in the cervical region of late symptomatic mice in the triton-insoluble post-synaptic fraction but not whole homogenates. Colocalisation experiments evidenced the expression of GluR1 and NR2A receptors in activated astrocytes from the cervical spinal cord of wobbler mice, GluR2 did not colocalise with GFAP positive cells. No differences were found in the expression of AMPA and NMDA receptor subunits in the lumbar tract of wobbler mice, where neither motoneuron loss nor reactive gliosis occurs.In late symptomatic wobbler mice altered levels of GluR1 and NR2A receptor subunits may be a consequence of motoneuron loss rather than an early feature of motoneuron vulnerability.Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motoneurons in the spinal cord, brainstem and motor cortex and leading to denervation, muscular atrophy, paralysis and premature death [1]. The disease is sporadic in approximately 90% of cases [2] and the correlation between the pathology and an identified gene mutation is known only in a small percentage of cases (2%) [3].Glutamate-induced excitotoxicity may be one of the main factors in ALS pathogenesis [4]. Both glial and neuronal glutamate transporters play a pivotal role in avoiding excitotoxicity by removing the excess of glutamate released into the synaptic cleft from presynaptic neurons and consequently preventing the overstimulation of post-synaptic glutamate receptors. Evidence of abnormal glutamate metabolism and impaired expression of the glial glutamate transporter 2 (EAAT2) in ALS patients suggests that glutamate-induced excitotoxicity plays a key role in generating this disease [5]. Glutamate overstimulation can act through both the N-methyl-D-aspartate (NMDA) receptors and the alpha-amino-3-hyd