Rm. Lopachin et al., 2,5-HEXANEDIONE ALTERS ELEMENTAL COMPOSITION AND WATER-CONTENT OF RATPERIPHERAL-NERVE MYELINATED AXONS, Journal of neurochemistry, 63(6), 1994, pp. 2266-2278
Effects of 2,5-hexanedione on elemental concentrations and water conte
nt of peripheral nerve myelinated axons were determined using electron
probe x-ray microanalysis. Axons (small, medium, and large) were anal
yzed in unfixed cryosections from rat tibial and proximal sciatic nerv
e samples. Animals were intoxicated with 2,5-hexanedione by two dosing
paradigms: intraperitoneal or oral. Regardless of the route of exposu
re, internodal axoplasm of small and medium axons from both nerve regi
ons exhibited selective, progressive reductions in dry weight K concen
trations and water content. When calculated on a wet weight basis, K l
evels were comparable to or slightly above control values in tibial ne
rve, whereas in sciatic nerve, small transient decreases in wet weight
K were evident. These changes in K and water correlated with the deve
lopment of axonal atrophy. The wet and dry weight internodal elemental
changes reported here do not suggest a metabolic or axolemmal defect,
but rather imply a homeostatic response possibly related to the proce
ss of axonal atrophy. Giant axonal swellings were primarily associated
with oral 2,5-hexanedione intoxication, and corresponding analyses re
vealed few changes in element or water content compared with control.
The absence of significant alterations in these swellings is consisten
t with mechanical expansion of the axon probably as a function of accu
mulating neurofilaments.