Brainstem Motoneuron Cell Groups that die in Amyotrophic Lateral Sclerosis are Rich in the GLT-1 Glutamate Transporter
Several studies have suggested that excessive Ca2+ influx into cells may underlie the selective destruction of motoneurons observed in the sporadic form of Amyotrophic Lateral Sclerosis (ALS)1–4. Consistent with this, in the cranial motor nuclei that survive better in sporadic ALS (i.e. oculomotor, trochlear and abducens motor nuclei), a high percentage of the motoneurons are enriched in the Ca2+ buffering protein parvalbumin in normal monkey and normal human brainstem5,6. In contrast, in the cranial motor nuclei that are dramatically affected in sporadic ALS (i.e. trigeminal, facial, and hypoglossal motor nuclei), only a low percentage of the motoneurons contain parvalbumin5,6. One possible clue as to why excessive Ca2+ influx into cells may occur in sporadic ALS has been provided by Rothstein and colleagues3. In brief, they have found a significant decrease of high-affinity glutamate transport in the motor cortex and spinal cord of sporadic ALS victims3, which seems to be due mainly to a profound loss of a specific glutamate transporter subtype, GLT-1, which is localized to astroglia7. A minor loss of another glutamate transporter subtype, EAAC1 (localized to neurons), also occurs in the motor cortex of ALS victims which may be secondary to the death of cortical neurons7. A defect in either glutamate transporter subtype would lead to an excess of extracellular glutamate in the vicinity of neurons depending on that transporter for glutamate clearance from the extracellular space.
KeywordsAmyotrophic Lateral Sclerosis Glutamate Transporter Motor Nucleus Sporadic Amyotrophic Lateral Sclerosis Medial Longitudinal Fasciculus
Unable to display preview. Download preview PDF.
- 5.A. Reiner, S. Anfinson, and G. Figueredo-Cardenas, Motoneurons that are resistant to ALS are preferentially enriched in the calcium binding protein parvalbumin, Neurosci. Abstr. 19:197 (1993).Google Scholar
- 6.A. Reiner, L. Medina, G. Figueredo-Cardenas, and S. Anfinson, Brainstem motoneuron pools that are selectively resistant in amyotrophic lateral sclerosis are preferentially enriched in parvalbumin: evidence from monkey brainstem for a calcium-mediated mechanism in sporadic ALS, Exp. Neurol. 131:239 (1995).PubMedCrossRefGoogle Scholar
- 7.J.D. othstein, M. Van Kammen, A.I. Levey, L. Martin, and R.W. Kuncl, Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis, Ann. Neurol 37 (1995) in press.Google Scholar
- 16.M. Dykes-Hoberg, L.J. Martin, A.I. Levey, D. Rye, N. Nash, L. Jin, R.W. Kuncl, and J.D. Rothstein, Cellular and ultrastructural localization of glutamate transporter subtypes in rat and human brain, Neurosci. Abstr. 20:927 (1994).Google Scholar