Cholinergic Function in Lumbar Aluminum Myelopathy

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.

Aluminum-induced acute cholinergic neurotoxicity in rat

“…Furthermore, the Al dose that causes neuronal damage in the brain is also unknown. Animals in previous studies in which various forms of Al salt were administered via various routes were usually treated multiple times (DeBoni et al, 1976;Hetnarski et al, 1980;Kosik et al, 1983;Gulya et al, 1990). Subsequently, the Al concentrations and neurochemical changes in the brain were measured.…”

“…Attempts have been made to develop an animal model of AD that could mimic the neuropathological changes and cholinergic deficit in the AD brain using Al as a cholinergic neurotoxin (Kosik et al, 1983;Wisniewski et al, 1990). Results have, however, been conflicting.…”

“…Al was noted to cause neurofibrillary degeneration in animals (DeBoni et al, 1976;Hetnarski et al, 1980), but some investigators reported Al had no effect on ChAT and AChE activities in the brain and spinal cord (Hetnarski et al, 1980;Johnson and Jope, 1987). Many other reports, however, favored Al causing reduction of cholinergic enzyme activity (Yates et al, 1980;Kosik et al, 1983;Boegman and Bates, 1984;Gulya et al, 1990). These data were obtained after chronic treatment of animals with Al administered through oral, intracisternal, intraventricular, and intraperitoneal routes.…”

Water Content of Aluminum, Dialysis Dementia, and Osteomalacia

“…The neurotoxicity of aluminum alternatively may involve alterations in the major postsynaptic enzymes of cholinergic neurotransmission (41). In support of this mechanism are the observations that aluminum inhibits choline transport in erythrocytes (42) and decreases choline acetyltransferase activity in nerve tissue (43). Aluminum has also been reported to inhibit cytosolic and mitochondrial hexokinase activities in rat brain and thus reduce carbohydrate utilization (44).…”

Effects of long-term in vitro exposure to aluminum, cadmium or lead on differentiation and cholinergic receptor expression in a human neuroblastoma cell line

“…The inhibition of cholinergic activity by aluminum in both in vivo and in vitro models (Johnson and Jope, 1986;Kosik et al, 1983;Miller and Levine, 1974) suggests that the cholinergic system may be an important target for aluminum neurotoxicity.…”