VACCINE

Molecular And Chemical Neuropathology • September 1997
Aluminum potentiates
glutamate-induced calcium accumulation
and iron-induced oxygen free radical formation
in primary neuronal cultures
Author information
Mundy WR1, Freudenrich TM, Kodavanti PR.
Neurotoxicology Division
US Environmental Protection Agency
Research Triangle Park, NC 27711, USA
Abstract
Aluminum is a neurotoxic metal that may be involved in the progression of
neurodegenerative diseases, including Alzheimer disease and amyotrophic lateral
sclerosis (ALS). Although the mechanism of action is not known, aluminum
has been shown to alter Ca2+ flux and homeostasis, and facilitate peroxidation
of membrane lipids. Since abnormal increases of intracellular Ca2+ and
oxygen free radicals have both been implicated in pathways leading to neurodegeneration,
we examined the effect of aluminum on these parameters in
vitro using primary cultures of cerebellar granule cells. Exposure to glutamate
(1-300 microM) caused a concentration-dependent uptake of 45Ca in granule
cells to a maximum of 280% of basal. Pretreatment with AlCl3 (1-1000 microM)
had no effect on 45Ca accumulation, but increased the uptake induced
by glutamate. Similarly, AlCl3 had no effect on intracellular free Ca2+ levels
measured using fluorescent probe fura-2, but potentiated the increase induced
by glutamate. The production of reactive oxygen species (ROS) was examined
using the fluorescent probe dichlorofluorescin. By itself, AlCl3 had little effect
on ROS production. However, AlCl3 pretreatment potentiated the ROS
production induced by 50 microM Fe2+. These results suggest that aluminum
may facilitate increases in intracellular Ca2+ and ROS, and potentially contribute
to neurotoxicity induced by other neurotoxicants.
“Aluminum is a neurotoxic metal
that may be involved in the progression
of neurodegenerative diseases, including
Alzheimer disease and amyotrophic lateral sclerosis ...
aluminum may facilitate increases in intracellular Ca2+
and ROS, and potentially contribute to
neurotoxicity induced by other neurotoxicants.”
http://www.ncbi.nlm.nih.gov/pubmed/9437657