| First Author | Fuchs A | Year | 2010 |
| Journal | J Neuropathol Exp Neurol | Volume | 69 |
| Issue | 10 | Pages | 1057-70 |
| PubMed ID | 20838240 | Mgi Jnum | J:357493 |
| Mgi Id | MGI:7763726 | Doi | 10.1097/NEN.0b013e3181f4dcef |
| Citation | Fuchs A, et al. (2010) Downregulation of the potassium chloride cotransporter KCC2 in vulnerable motoneurons in the SOD1-G93A mouse model of amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 69(10):1057-70 |
| abstractText | The balance between excitatory and inhibitory synaptic inputs is critical for the physiological control of motoneurons. The maintenance of a low-intracellular chloride concentration by the potassium chloride cotransporter 2 (KCC2) is essential for the efficacy of fast synaptic inhibition of mature motoneurons in response to the activation of ionotropic gamma-aminobutyric acid A and glycine receptors. Altered synaptic balance and excitotoxicity have been proposed as candidate pathophysiological processes in amyotrophic lateral sclerosis (ALS). Therefore, we investigated the expression patterns of KCC2 and its functional opponent, the chloride influx-mediating sodium-potassium chloride cotransporter 1 (NKCC1), in the superoxide dismutase 1 (SOD1-G93A) mouse model of ALS. We detected reduced KCC2 messenger RNA levels and less membrane-bound KCC2 immunoreactivity in ALS-vulnerable motoneurons in lumbar spinal cord and hypoglossal nuclei of SOD1-G93A mice but not in degeneration-resistant oculomotor nuclei. Downregulation of KCC2 started during late presymptomatic stages and accelerated in parallel to hind limb and tongue motor function deficits. In contrast, NKCC1 messenger RNA levels were unaltered in postnatal lumbar spinal cord motoneurons. Our data indicate that reductions in KCC2 gene expression may contribute to selective motor deficits and disease progression in vulnerable motoneurons in a mouse model of ALS. |
