Title: Modulation of rat hippocampal neurons by H2O2-mediated oxidative stress
Authors: Gerich, Florian
Müller, M #
Issue Date: 2007
Conference: Göttingen Meeting of the German Neuroscience Society 2007 edition:7 location:Göttingen date:29 March - 01 April 2007
Article number: T35-7B
Abstract: Superoxide released from dysfunctioning mitochondria is converted to H2O2, which modulates
redox-sensitive proteins. Such redox signaling occurs under pathophysiological conditions, but it is also part
of normal signaling. To identify putative signaling pathways involved in such redox signaling, we analyzed
the H2O2-mediated responses of hippocampal neurons. Oxidation of the redox-sensitive dyes hydroethidium
and dichlorofluorescein confirmed the membrane permeability of H2O2 in cultured neurons and acute slices,
thus H2O2 may not only act at its generation site, but may affect neighboring cells as well. Application of 1-5
mM H2O2 postponed the onset of hypoxic spreading depression, but did not depress basal synaptic function or
plasticity. Mitochondria depolarized only slightly in response to 1 mM H2O2, directed mitochondrial motility
was arrested, and cellular NADH as well FADH2 were apparently directly oxidized. Sharp electrode
recordings revealed a hyperpolarization of CA1 pyramidal neurons paralleled by a decrease in input
resistance, suggesting that H2O2 activates K+ channels. In cultured hippocampal neurons low concentrations
of H2O2 (0.2 mM) moderately increased the intracellular Ca2+ concentration. This Ca2+ rise was not
prevented by Ca2+-free solution, mitochondrial uncoupling by 1 μM FCCP or Fe2+-chelators. Yet it was
depressed by 1-5 μM thapsigargin, 10 μM ruthenium red or 20 μM dantrolene. Ryanodine applied in low
concentrations (1 μM) mimicked the H2O2-evoked Ca2+ transients, while higher concentrations (25 μM)
depressed them. In conclusion, low levels of H2O2 release Ca2+ from the endoplasmic reticulum via
ryanodine receptors. Such modulation of Ca2+ sequestration by redox state and ROS levels as well as the
redox-dependent activation of K+ channels could play a pivotal role in the sensing of metabolic disturbances
and the adjustment of neuronal function to oxidative stress.
Publication status: published
KU Leuven publication type: IMa
Appears in Collections:Laboratory for Experimental Psychology
# (joint) last author

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