Axonal dystrophy in monkey spinal ganglia: Involvement of the initial segment of axons

Abstract

Examination of spinal ganglia of ageing and old Japanese monkeys, Macaca fuscata, by light microscopy and electron microscopy revealed unidentified pathology of the axon initial segment. Although the incidence of this change is infrequent in any one histological section of ganglion, its morphology is quite remarkable. The change is characterized by a progressive swelling of the unmyelinated portion of axon followed by continuous involvement of the first myelin segment. Neurofilaments proliferate in rather randomly oriented bundles within the affected axons accompanied with a considerable amount of mitochondria. The axons, originally 3–5 um in diameter, thus become nodularly varicose and become as thick as 20 um or more in diameter. The second stage of the axonal pathology is characterized by massive dense accumulation of tiny vesicular granules which infiltrates and/or replaces the neurofilament mass, almost fills the whole axon and the affected axons could result in a thickness of 70 um or more in diameter (i.e. larger than the mother perikaryon itself). The third stage of the axonal pathology is characterized by a catabolic transformation of those dense massive aggregates of the vesicular granules into irregular patches of amorphous electron dense substance. Smooth endoplasmic reticulum may make a focus of proliferation within the affected axon, but its development is relatively poor and restricted. It is surprising that the mother perikaryon of the affected axon initial segment remains as a rule quite normal in appearance. It is also remarkable that the part of the axon which is distal to the swelling remains viable, apparently for a long time. The significance of this axonal pathology is discussed in relation to ageing and diabetic axonal dystrophy in the sympathetic ganglia, and to ageing axonal dystrophy in the gracile nucleus.