| First Author | Pardo AC | Year | 2006 |
| Journal | Exp Neurol | Volume | 201 |
| Issue | 1 | Pages | 120-30 |
| PubMed ID | 16753145 | Mgi Jnum | J:144898 |
| Mgi Id | MGI:3832149 | Doi | 10.1016/j.expneurol.2006.03.028 |
| Citation | Pardo AC, et al. (2006) Loss of the astrocyte glutamate transporter GLT1 modifies disease in SOD1(G93A) mice. Exp Neurol 201(1):120-30 |
| abstractText | Recent studies have highlighted the role of astrocytes in the development of motor neuron disease in animal models. The astrocyte glutamate transporter GLT1 is responsible for a significant portion of glutamate transport from the synaptic cleft; regulating synaptic transmission and preventing glutamate excitotoxicity. While previous studies have demonstrated reductions in GLT1 with SOD1-mediated disease progression, it is not well established whether a reduction in this astrocyte-specific transporter alters the pathobiology of motor neuron degeneration in the SOD1(G93A) mouse. In order to address this possible astrocyte-specific influence, we crossed the SOD1(G93A) mouse line with a mouse heterozygous for GLT1 (GLT1+/-) exhibiting a significant reduction in transporter protein. Mice that carried both the SOD1 mutation and a reduced amount of GLT1 (SOD1(G93A)/GLT1+/-) exhibited an increase in the rate of motor decline accompanied by earlier motor neuron loss when compared with SOD1(G93A) mice. A modest reduction in survival was also noted in these mice. Dramatic losses of the GLT1 protein and reduced glutamate transport in the lumbar spinal cords of the SOD1(G93A)/GLT1+/- animals were also observed. GLT1 was not significantly changed in cortices from these animals suggesting that the effect of mutant SOD1 on GLT1 production/function was largely targeted to spinal cord rather than cortical astrocytes. This study suggests that astrocytes, and the astrocyte glutamate transporter GLT1, play a role in modifying disease progression and motor neuron loss in this model. |
