Abnormalities of central axons in a dysmyelinative rat mutant

The absence of normal myelin from the CNS of the dysmyelinative rat mutant, md, is associated with axonal abnormalities including organelle-poor and organelle-rich spheroids (OPS and ORS, respectively), wrinkling of the axolemma, persistence of glycogen aggregates and vacuoles in cerebellar mossy fiber terminals, and coalescence of synaptic vesicles in terminal boutons of the nucleus interpositus. OPS have a special predilection for medullary pyramid and the axons of Purkinje cells and further differ from ORS in their possession of nematosomes and in their lack of neurofilaments, microtubules, and degenerating mitochondria. Purkinje cells of md fail to increase in size after 30 days postnatal age and, unlike these neurons in normal neonatal rats, may have massed or dispersed granules of cytoplasmic glycogen which persist for at least 86 days postnatally. Morphometric study of axons of medullary pyramid and cervical corticospinal tract at 19-43 days of age shows a shift in frequency to axons of smaller size in md, as compared to age-matched controls, except that approximately 1% of md axons are larger than any encountered in controls. Finally, the pyramidal axons of md at 43 days of age have a significantly larger area of axoplasm occupied by mitochondria than obtains for the control condition. We conclude that the described abnormalities are secondary to the lack of a myelin investment and/or the loss of oligodendrocytes.