Acute action of rotenone on nigral dopaminergic neurons – involvement of reactive oxygen species and disruption of Ca2+ homeostasis

@article{Freestone2009AcuteAO,
  title={Acute action of rotenone on nigral dopaminergic neurons – involvement of reactive oxygen species and disruption of Ca2+ homeostasis},
  author={Peter S. Freestone and Kenny K. H. Chung and Ezia Guatteo and Nicola Biagio Mercuri and Louise Frances Basford Nicholson and Janusz Lipski},
  journal={European Journal of Neuroscience},
  year={2009},
  volume={30}
}
Rotenone is a toxin used to generate animal models of Parkinson’s disease; however, the mechanisms of toxicity in substantia nigra pars compacta (SNc) neurons have not been well characterized. We have investigated rotenone (0.05–1 μm) effects on SNc neurons in acute rat midbrain slices, using whole‐cell patch‐clamp recording combined with microfluorometry. Rotenone evoked a tolbutamide‐sensitive outward current (94 ± 15 pA) associated with increases in intracellular [Ca2+] ([Ca2+]i) (73.8 ± 7.7… Expand
Mitochondrial uncoupling agents antagonize rotenone actions in rat substantia nigra dopamine neurons
TLDR
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TLDR
The results indicate that the initial cellular events that lead to activation of cell death pathways by MPP(+) are complex and include KATP, and dopamine-dependent components, and show that the inhibitory effect of the toxin is independent of Ih block. Expand
Multiple Actions of Rotenone, an Inhibitor of Mitochondrial Respiratory Chain, on Ionic Currents and Miniature End-Plate Potential in Mouse Hippocampal (mHippoE-14) Neurons
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Paradoxical lower sensitivity of Locus Coeruleus than Substantia Nigra pars compacta neurons to acute actions of rotenone
TLDR
It is demonstrated that rotenone inhibits the activity of LC neurons mainly by activating KATP channels, and increases [Ca2 +]i via TRPM2 channels, which is paradoxically less sensitive to acute effects of this parkinsonian toxin. Expand
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TRPM2 Promotes Neurotoxin MPP+/MPTP-Induced Cell Death
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A novel role for TRPM2 expression and function is shown in MPP+-induced dopaminergic neuronal cell death by pharmacological inhibition or knockdown of TR PM2 using siRNA, which showed an increased protection by preventing MPP-induced Ca2+ increase and inhibited apoptosis. Expand
Glutathione Modulates Ca2+ Influx and Oxidative Toxicity Through TRPM2 Channel in Rat Dorsal Root Ganglion Neurons
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The protective role of 2-APB and GSH on Ca2+ influx through a TRPM2 channel in intracellular GSH depleted DRG neurons is observed and is relevant to the etiology of neuropathology in DRg neurons. Expand
Glutathione Modulates Ca 2+ Influx and Oxidative Toxicity Through TRPM2 Channel in Rat Dorsal Root Ganglion Neurons
Glutathione (GSH) is the most abundant thiol antioxidant in mammalian cells and maintains thiol redox in the cells. GSH depletion has been implicated in the neurobiology of sensory neurons. BecauseExpand
Aminoethoxydiphenyl Borate and Flufenamic Acid Inhibit Ca2+ Influx Through TRPM2 Channels in Rat Dorsal Root Ganglion Neurons Activated by ADP-Ribose and Rotenone
TLDR
TRPM2 channels were constitutively activated by ADPR and rotenone, and 2-APB and FFA induced an inhibitory effect on TRPM2 cation channel currents in rat DRG neurons, which have broad application to the etiology of neuropathic pain and diseases ofDRG neurons. Expand
Crosstalk between Ca2+ signaling and mitochondrial H2O2 is required for rotenone inhibition of mTOR signaling pathway leading to neuronal apoptosis
TLDR
It is shown that rotenone elevates intracellular free calcium ion level, and activates CaMKII, resulting in inhibition of mTOR signaling and induction of neuronal apoptosis, and how to control over-elevation of intrACEllular Ca2+ and overproduction of mitochondrial H2O2 may be a new approach to deal with the neurotoxicity of roten one. Expand
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