Studies on myelination and demyelination

of paper presented at the first annual meeting of the Section on Neurochemistry, American Academy of Neurology. Boston, A p d 26. 1957. Supported by a grant from the National Multiple Sclerosis Society. 'Work perfornied during the tenure of a Lederle Medical Faculty award. SECTION ON NEUROCHEMISTRY 89 rat several proximo-distal gradients were observed. If the upper half of the sciatic nerve is compared with the tibial nerve, the latter is found to contain 20 per cent less lipid, its oxygen uptake is 13 per cent lower, and acetate incorporation into the lipids is also 15 per cent lower. These findings may be of relevance in the pathogenesis of the “peripheral neuropathies.” WALLERIAN DEGENERATION Bilateral section of the sciatics was performed in 128 rats. The animals were killed at intervals varying between four hours and 50 days; particular attention was given to the early stages of degeneration. Oxygen uptake (referred to dry weight) was reduced to 75 per cent of normal after 24 hours, then increased to 200 per cent by the tenth day. Incorporation of acetate into the lipids dropped to 30 per cent of normal during the first five days; by the end of four weeks it rose above 300 per cent. This result in rats with acetateC 1 4 is similar to that observed by Magee and Rossiter4 using radioactive phosphate. In the proximal stump, excluding the regenerating cone, incorporation of acetate was also reduced by approximately one-third 12 days after section. DEMYELINATION INDUCED BY MIPAFOX Rats treated with biweekly subcutaneous injections of Mipafox (bis-monoisopropylaminofluorophosphine oxide) over three to four months developed weakness of the hind limbs and a typical peripheral neuropathy characterized by degeneration, histologically of Wallerian type, in the distal half of the tibial nerve. At this stage, lipogenesis from acetate was found to be depressed in the upper half of the sciatic and enhanced in the tibial nerve (similar to the picture in early and late stages of Wallerian degeneration, respectively). In hens killed 20 to 25 days after injection of the same drug, demyelination of white matter was studied on isolated funiculi stripped from the spinal cord. Acetate incorporation into the lipids was depressed in direct proportion to the extent of demyelination observed histologically within the tracts. In the sciatic nerves of the same hens acetate incorporation was reduced to 43.7 per cent (P < 0.01) of normal. These studies on the patterns of lipogenesis in nervous tissue, using various lipid building blocks, are continuing. Subjects currently being investigated are: the changes in longitudinal tracts of the spinal cord of the rat at varying intervals after surgical section, and the interference with lipogenesis by various chemical agents in vitro.