Impaired tolerance to repetitive hypoxia in hippocampal slices of Cu,Zn superoxide dismutase transgenic mice

Energy metabolism is impaired in the Cu,Zn superoxide dismutase transgenic mouse model of amyotrophic lateral sclerosis. The goal was to investigate t olerance against single and repetitive hypoxia in C57BGSJL-TSN(SOD1-G93A)1G UR mice (G93A mice). Posthypoxic recovery (15 min hypoxia, 45 min recovery) of population spike amplitude in hippocampal region CA1 was 38 +/- 29% (me an +/- SD) in controls and 67 +/- 41% (ns) in G93A mice at day 40. Upon in vivo pretreatment with 20 mg/kg 3-nitropropionate posthypoxic recovery incr eased to 82 +/- 32% (P < 0.01) in controls and decreased to 35 +/- 33% in G 93A mice (P < 0.05 to pretreated controls). Results at day 80 and 110 were similar. We conclude that G93A mice show a long-lasting impairment to susta in repetitive hypoxic episodes whereas tolerance to a single hypoxic episod e is comparable to controls. (C) 1999 Elsevier Science Ireland Ltd. All rig hts reserved.