| First Author | Damiano M | Year | 2006 |
| Journal | J Neurochem | Volume | 96 |
| Issue | 5 | Pages | 1349-61 |
| PubMed ID | 16478527 | Mgi Jnum | J:106152 |
| Mgi Id | MGI:3617682 | Doi | 10.1111/j.1471-4159.2006.03619.x |
| Citation | Damiano M, et al. (2006) Neural mitochondrial Ca capacity impairment precedes the onset of motor symptoms in G93A Cu/Zn-superoxide dismutase mutant mice. J Neurochem 96(5):1349-61 |
| abstractText | Mitochondrial respiratory chain dysfunction, impaired intracellular Ca(2+) homeostasis and activation of the mitochondrial apoptotic pathway are pathological hallmarks in animal and cellular models of familial amyotrophic lateral sclerosis associated with Cu/Zn-superoxide dismutase mutations. Although intracellular Ca(2+) homeostasis is thought to be intimately associated with mitochondrial functions, the temporal and causal correlation between mitochondrial Ca(2+) uptake dysfunction and motor neuron death in familial amyotrophic lateral sclerosis remains to be established. We investigated mitochondrial Ca(2+) handling in isolated brain, spinal cord and liver of mutant Cu/Zn-superoxide dismutase transgenic mice at different disease stages. In G93A mutant transgenic mice, we found a significant decrease in mitochondrial Ca(2+) loading capacity in brain and spinal cord, as compared with age-matched controls, very early on in the course of the disease, long before the onset of motor weakness and massive neuronal death. Ca(2+) loading capacity was not significantly changed in liver G93A mitochondria. We also confirmed Ca(2+) capacity impairment in spinal cord mitochondria from a different line of mice expressing G85R mutant Cu/Zn-superoxide dismutase. In excitable cells, such as motor neurons, mitochondria play an important role in handling rapid cytosolic Ca(2+) transients. Thus, mitochondrial dysfunction and Ca(2+)-mediated excitotoxicity are likely to be interconnected mechanisms that contribute to neuronal degeneration in familial amyotrophic lateral sclerosis. |
