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Alternatives to Laboratory Animals - ATLA

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Effects of Aluminium and Lead on ATPase Activity of Knockout GDNF+/ Mouse Cerebral Synaptosomes In Vitro

T. Kohila and H. Tähti

In this in vitro study, changes in the activity of the neural membrane integral protein, ATPase, were recorded after the exposure of isolated synaptosomes to different concentrations of aluminium and lead. Both total ATPase activity and Mg2+-ATPase activity were studied. A specific mouse strain, heterozygous for a glial cell line-derived neurotrophic factor (GDNF), and the corresponding wildtype mouse cerebral tissue, were used for the synaptosome isolations. The ATPase activities of the GDNF+/– mouse synaptosomes were compared with those of wild-type synaptosomes. The decrease in total ATPase activity was similar in both types of synaptosomes, but after exposure to aluminium, the decrease of Mg2+-ATPase activity in the GDNF+/– synaptosomes was smaller than that in the wild-type synaptosomes. After exposure to lead, the protective effect of GDNF was not so clear. The synaptosomal effects of lead were already found at concentrations lower than those where cell toxicity appeared in SHSY5Y cell cultures. Thus, synaptosomal ATPase activity was considered to be a sensitive marker for the detection of lead-induced neurotoxicity.