| First Author | Bowerman M | Year | 2017 |
| Journal | Neurobiol Dis | Volume | 106 |
| Pages | 35-48 | PubMed ID | 28647557 |
| Mgi Jnum | J:260635 | Mgi Id | MGI:6142711 |
| Doi | 10.1016/j.nbd.2017.06.013 | Citation | Bowerman M, et al. (2017) KCC3 loss-of-function contributes to Andermann syndrome by inducing activity-dependent neuromuscular junction defects. Neurobiol Dis 106:35-48 |
| abstractText | Loss-of-function mutations in the potassium-chloride cotransporter KCC3 lead to Andermann syndrome, a severe sensorimotor neuropathy characterized by areflexia, amyotrophy and locomotor abnormalities. The molecular events responsible for axonal loss remain poorly understood. Here, we establish that global or neuron-specific KCC3 loss-of-function in mice leads to early neuromuscular junction (NMJ) abnormalities and muscular atrophy that are consistent with the pre-synaptic neurotransmission defects observed in patients. KCC3 depletion does not modify chloride handling, but promotes an abnormal electrical activity among primary motoneurons and mislocalization of Na(+)/K(+)-ATPase alpha1 in spinal cord motoneurons. Moreover, the activity-targeting drug carbamazepine restores Na(+)/K(+)-ATPase alpha1 localization and reduces NMJ denervation in Slc12a6(-/-) mice. We here propose that abnormal motoneuron electrical activity contributes to the peripheral neuropathy observed in Andermann syndrome. |
