Involvement of the ubiquitin-proteasome system in the early stages of wallerian degeneration

Local axon degeneration is a common pathological feature of many neurodegenerative diseases and peripheral neuropathies. While it is believed to operate with an apoptosis-independent molecular program, the underlying molecular mechanisms are largely unknown. In this study, we used the degeneration of transected axons, termed "Wallerian degeneration," as a model to examine the possible involvement of the ubiquitin proteasome system (UPS). Inhibiting UPS activity by both pharmacological and genetic means profoundly delays axon degeneration both in vitro and in vivo. In addition, we found that the fragmentation of microtubules is the earliest detectable change in axons undergoing Wallerian degeneration, which among other degenerative events, can be delayed by proteasome inhibitors. Interestingly, similar to transected axons, degeneration of axons from nerve growth factor (NGF)-deprived sympathetic neurons could also be suppressed by proteasome inhibitors. Our findings suggest a possibility that inhibiting UPS activity may serve to retard axon degeneration in pathological conditions.     

The origin of reactive cells in retrograde and wallerian degeneration

Summary In order to examine the possible haematogenous origin of phagocytes in anterograde and retrograde degeneration, rabbit peritoneal macrophages were labeled in vitro with ³H-DFP and injected intravenously into host animals. Four or five days prior to the injection, the facial nerve was avulsed and the sciatic nerve ligated in five recipients. The animals were killed 24 h after the injection of the macrophages. Labeled cells were found in that part of the sciatic nerve which was mechanically damaged and in the liver and spleen but not in areas with retrograde or Wallerian degeneration. The possible interpretation of these findings is discussed.The present experiments were performed by M.O. after suggestions by A.T. These studies were supported by a grant from the Deutsche Forschungsgemeinschaft     

Neuroglia of the adult rat optic nerve in the course of wallerian degeneration

The neurological reactions in Wallerian degeneration have been studied by electron microscopy in the optic nerve of adult albino rats from 7 to 120 days after unilateral enucleation. Reactive astrocytes contained abundant dense bodies, numerous microtubules and hyperplastic glial filaments. These astrocytes also assisted phagocytosis of degenerated myelin sheaths and in glial scar formation. Oligodendrocytes disconnected their cytoplasmic extensions, which were phagocytosed by microglial cells and astrocytes, by increased production of lysosomes. Microglial cells consisted of crinkled, long, rough endoplasmic reticula, several highly-active Golgi complexes, laminar inclusions and globoid lipid droplets. Microglia engulfed and lysed the disintegrated axons and myelin sheaths.     

Nerve impulse propagation affected by sol-gel changes in axoplasm

Changes in temperature and pressure alter the gel-sol state of protoplasm. The degree of gelation relates to the structural properties of protoplasm and since the propagation velocity of a nerve impulse depends on the apparent modulus of elasticity, altering temperature and pressure changes the velocity of the impulse.     

Histone changes during degeneration and regeneration of the pancreas

1. Changes in the microstructure of histones from the pancreas were followed in rats given ethionine while on a protein-free diet. The lysine-rich histone F1 and the other histones extracted subsequently with 250mm-hydrochloric acid were isolated. When the ethionine-treated rats returned to the stock diet, regeneration of the pancreas was accompanied by an immediate increase in phosphate content of the total histone extract from which histone F1 had been removed. After 3-4 days there was a further increase in the phosphate content of this extract, and also in that of histone F1. 2. Similar changes in the phosphate and thiol+disulphide content of pancreas histones other than F1 were produced by starvation and re-feeding.