Jm. Godfraind et al., Hypoxia on hippocampal slices from mice deficient in dystrophin (mdx) and isoforms (mdx(3cv)), J CEREBR B, 20(1), 2000, pp. 145-152
Slices from control C57, mdx, and mdx(3cv) mice were made hypoxic until bot
h field excitatory postsynaptic potential (fEPSP) and presynaptic afferent
volley (AV) disappeared (H1). After reoxygenation and recovery of fEPSP, a
second and longer hypoxic test (H2) lasted 3 minutes beyond the time requir
ed to block AV. When slices were kept in 10 mmol/L glucose, H1 abolished AV
37 and 19% earlier in slices from mdx and mdx(3cv) mutants than in control
slices (where ill = 12 +/- 4.6 minutes, mean +/- SD). During H2 or when sl
ices were kept in 4 mmol/L glucose, AV vanished even more quickly, but the
times to block did not differ significantly between slices from controls an
d mutants. After reoxygenation, AV fully recovered in most slices. Rates of
blockade of fEPSPs were comparable in all slices, and most fEPSPs recovere
d fully after H1. But even in the presence of 10 mmol/L glucose, the second
hypoxia suppressed fEPSPs irreversibly in some slices: 2 of 10 from contro
l, 3 of 7 from mdx, and 1 of 6 from mdx(3cv) mice. Most slices in 4 mmol/L
glucose showed no recovery at all: six of seven from control, three of five
from mdx, and four of five from mdx(3cv) mice. Thus, slices from mdx mice
were more susceptible than other slices to irreversible hypoxic failure whe
n slices were kept in 10 mmol/L glucose, but they were less susceptible tha
n other slices when kept in 4 mmol/L glucose. In conclusion, the lack of fu
ll-length dystrophin (427 kDa) predisposes to quicker loss of nerve conduct
ion in slices from mdx and mdx(3cv) mutants and improved posthypoxic recove
ry of fEPSPs in 4 mmol/L glucose in slices from mdx but not mdx(3cv) mutant
s, perhaps because the 70-kDa and other C-terminal isoforms are still prese
nt in mdx mice.