Neural mitochondrial Ca2+ capacity impairment precedes the onset of motor symptoms in G93A Cu/Zn‐superoxide dismutase mutant mice

• DOI: 10.1111/j.1471-4159.2006.03619.x
• Publication Date: 2006-01-30T17:11:09Z
• Authors: Maria Damiano; Anatoly A. Starkov; Susanne Petri; Kathuna Kipiani; Mahmoud Kiaei; Marina Mattiazzi; M. Flint Beal; Giovanni Manfredi
• Keywords: Excitotoxicity

Abstract Mitochondrial respiratory chain dysfunction, impaired intracellular Ca 2+ homeostasis and activation of the mitochondrial apoptotic pathway are pathological hallmarks in animal cellular models familial amyotrophic lateral sclerosis associated with Cu/Zn‐superoxide dismutase mutations. Although is thought to be intimately functions, temporal causal correlation between uptake dysfunction motor neuron death remains established. We investigated handling isolated brain, spinal cord liver mutant transgenic mice at different disease stages. In G93A mice, we found a significant decrease loading capacity brain cord, as compared age‐matched controls, very early on course disease, long before onset weakness massive neuronal death. was not significantly changed mitochondria. also confirmed impairment mitochondria from line expressing G85R dismutase. excitable cells, such neurons, play an important role rapid cytosolic transients. Thus, ‐mediated excitotoxicity likely interconnected mechanisms that contribute degeneration sclerosis.