2,5-HEXANEDIONE ALTERS ELEMENTAL COMPOSITION AND WATER-CONTENT OF RATPERIPHERAL-NERVE MYELINATED AXONS

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.