Effects of hydrogen peroxide and calcium on intracellular ATP levels in different neuronal cell types

BACKROUND: Studies suggest that hippocampal neurons may be more vulnerable to oxida-tive stress than cortical cells. Since disturbed ATP-metabolism may be involved in such a dif-ferential vulnerability of neurons, we here evaluated the effects of hydrogen peroxide (H2O2-) induced oxidative stress on neuronal energy metabolism in different neuronal systems. Methods: Using primary cortical and hippocampal neurons as well as immortalized hippo-campal HT22 cells, we determined intracellular ATP levels and accompanying cell death after oxidative challenge with H2O2. Furthermore, the effects of a long-time incubation with H2O2 on the viability of HT22 cells were evaluated with a modified MTT-reduction assay. Results: H2O2-incubation lead to decreased intracellular ATP levels in a dose- and time-dependent manner in all neuronal cell systems tested. These effects were pronounced in pri-mary hippocampal neurons and less detectable in HT22 cells. However, even long-time incu-bation with comparable H2O2 concentrations did not obligatory lead to cell death in the MTT assay. Conclusions: Our data underline that H2O2-treatment is able to disturb intracellular en-ergy metabolism especially in primary hippocampal neurons. Decreased ATP levels do not obligatory induce cell death but may explain the selective neuronal vulnerability.