| First Author | Dachs E | Year | 2013 |
| Journal | Neuroscience | Volume | 250 |
| Pages | 417-33 | PubMed ID | 23876328 |
| Mgi Jnum | J:207041 | Mgi Id | MGI:5554332 |
| Doi | 10.1016/j.neuroscience.2013.07.026 | Citation | Dachs E, et al. (2013) Chronic treatment with lithium does not improve neuromuscular phenotype in a mouse model of severe spinal muscular atrophy. Neuroscience 250:417-33 |
| abstractText | Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by defective levels of the survival motor neuron (SMN) protein. SMA causes spinal motoneuron (MN) loss, and progressive muscle weakness and paralysis. Currently, there is no effective therapy to cure this disease. Although different strategies focused on increasing the expression of functional SMN protein have been assayed, numerous SMN-independent therapeutic approaches have been demonstrated to have potential effectiveness in improving the SMA phenotype in mouse models and clinical trials. Recent works have shown that compounds which inhibit GSK-3beta activity are effective in promoting MN survival and ameliorating lifespan in models of MN diseases including SMA. Taking into account the reported neuroprotective actions of lithium (Li) through the inhibition of GSK-3beta in different studies, we tested here its potential efficiency as a therapeutic agent in a mouse model of severe SMA (SMNDelta7 mice). We show that the chronic treatment with Li initiated before the appearance of disease symptoms, although inhibited GSK-3beta, did not improve the median survival, motor behavior, and spinal MN loss linked to SMA. Li administration did not either ameliorate the microglial and astroglial reaction in the spinal cord or the depletion of glutamatergic synapses on MNs observed in SMNDelta7 animals. Moreover, Li treatment did not mitigate muscle atrophy or calcitonin gene-related peptide (CGRP) downregulation in the neuromuscular junctions linked to the disease. However, a significant reduction in apoptotic cell death found in the skeletal muscle of SMA mice was observed after Li treatment. |
