Abstract
To determine whether perikaryal neurofilamentous accumulation in cholinergic neurons is associated with a deficit in cholinergic function, we developed a new model of aluminum-induced neurofibrillary degeneration, referred to as focal lumbar aluminum myelopathy. The model is produced by direct intramedullary microinjection of AlCl3, which results in a characteristic neurological syndrome. Four weeks after injections, affected rabbits show extensive neurofilamentous lesions of both large and small neurons in the lumbar spinal cord, including a majority of anterior horn cells. These animals are capable of long-term survival. Posterior tibial nerve morphometry in these rabbits revealed no significant loss of myelinated fibers. Choline acetyltransferase (ChAT) activity in the sciatic nerve was decreased 39%, from 45.70 ± 2.36 nmol ACh/hour/3-mm segment in acid-injected controls to 17.72 ± 1.94 in aluminum-intoxicated rabbits. The rate of accumulation of ChAT activity proximal to a sciatic nerve ligature was significantly greater in the aluminum-treated rabbits, although the total amount of ChAT activity accumulating in a 24-hour period did not differ from controls. We conclude that aluminum-induced accumulation of neurofilaments in cholinergic perikarya is associated with a sharp decrease of ChAT activity in the axons of those cells and possibly with a compensatory increase in the rate of delivery of the enzyme.
