THE FRAGMENTED NEURONAL GOLGI-APPARATUS IN AMYOTROPHIC-LATERAL-SCLEROSIS INCLUDES THE TRANS-GOLGI-NETWORK - FUNCTIONAL IMPLICATIONS

The Golgi apparatus (GA) of spinal cord motor neurons is fragmented in sporadic amyotrophic lateral sclerosis (ALS), and in asymptomatic and symptomatic transgenic mice expressing the G93A mutation of the gene of the human Cu,Zn superoxide dismutase, found in certain cases of fam ilial ALS (FALS) [Gonatas NK (1994) Am J Pathol 145:751-761; Mourelato s Z, et al. (1996) Proc Natl Acad Sci USA 93:5472-5477]. A similar fra gmentation of the GA has been described in cells treated with microtub ule-depolymerizing drugs, where the organelle is functional and contai ns both Golgi stacks and trans-Golgi network (TGN), the compartment of exit and targeting of proteins processed by the GA. To gain a better definition of the structure of the fragmented neuronal GA in ALS, four cases of sporadic ALS with numerous Bunina bodies in spinal cord moto r neurons were stained with antibodies against human TGN and against t he lumenal and cytoplasmic domains of MG160, a protein of the medial c isternae of the GA. The fragmented GA was stained with the three antib odies, indicating the presence of both Golgi stacks and TGN. Furthermo re, the staining of the fragmented GA by the antiserum against the cyt oplasmic domain of MG160 indicates that the fragmentation of the GA is not the result of a terminal and global cytoplasmic lytic event. The Bunina bodies were not stained by the anti-MG160 antibodies, suggestin g that they are not derived from the GA. The perikarya of neurons with fragmented GA showed normal immunoreactivity with antibodies against the heavy neurofilament subunit and alpha-tubulin. However, because of the lack of appropriate antibodies the localization of proteins such as spectrin, ankyrin, centractin and others which link the microtubule s with the GA were not done. The findings support the hypothesis that, in ALS, the fragmented neuronal GA is functional. Additional work wit h animal models of ALS may establish whether the fragmentation of the GA is a sign of early degeneration or a compensatory reaction of the i njured motor neuron.