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These changes include astrogliosis, fragmentation of Golgi apparatus, SOD1 aggregation and vacuolar degeneration [ 7 11 12 13 14 ] . Vacuolar degeneration is most prominent at the onset of the disease and precedes motoneuron death by two to three months [ 15 ] . Although the high expresser line of SOD1 G93Ashowed vacuoles derived from both endoplasmic reticulum and mitochondria [ 13 ] , the lower expresser line of SOD1 G93A, which more closely mimics the human SOD1 levels [ 16 ] , showed vacuoles that are nearly all developed from degenerating mitochondria [ 15 17 ] . Mitochondrial vacuolation was also reported in another transgenic line SOD1 G37R [ 7 ] .