title: Acute exposure to the mitochondrial complex I toxin rotenone impairs synaptic long-term potentiation in rat hippocampal slices.
abstract: OBJECTIVE
  To evaluate the acute effects of the mitochondrial complex I inhibitor rotenone on rat hippocampal synaptic plasticity.
  
  
  METHODS
  Electrophysiological field potential recordings were used to measure basal synaptic transmission and synaptic plasticity in rat coronal hippocampal slices. Synaptic long-term potentiation (LTP) was induced by high-frequency stimulation (100 Hz, 1 second × 3 at an interval of 20 seconds). In addition, mitochondrial complex I function was measured using MitoSOX imaging in mitochondrial preparations.
  
  
  RESULTS
  Acute exposure of hippocampal slices to 50 nM rotenone for 1 h did not alter basal CA3-CA1 synaptic transmission though 500 nM rotenone significantly reduced basal synaptic transmission. However, 50 nM rotenone significantly impaired LTP and this rotenone's effect was prevented by co-application of rotenone plus the ketones acetoacetate and β-hydroxybutyrate (1 mM each). Finally, we measured mitochondrial function using MitoSOX imaging in mitochondrial preparations and found that 50 nM rotenone partially reduced mitochondrial function whereas 500 nM rotenone completely eliminated mitochondrial function.
  
  
  CONCLUSIONS
  Our findings suggest that mitochondrial activity driven by complex I is a sensitive modulator of synaptic plasticity in the hippocampus. Acute exposure of the hippocampus to rotenone eliminates complex I function and in turn impairs LTP.
authors.affiliation: Department of Physiology, Shantou University Medical College, Shantou, China.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Kimura
authors.forename: Lu-Yao
authors.initials: LY
authors.lastname: Ma
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.forename: Dharshaun
authors.initials: D
authors.lastname: Turner
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Shen
authors.forename: Kevin
authors.initials: K
authors.lastname: Ellsworth
authors.forename: Makoto
authors.initials: M
authors.lastname: Wakui
authors.forename: Marwan
authors.initials: M
authors.lastname: Maalouf
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000494:pharmacology; D000090:Acetoacetates / Q000494:pharmacology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects; D042967:Electron Transport Complex I / Q000187:drug effects*; D055724:Electrophysiological Phenomena; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D007659:Ketones / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012402:Rotenone / Q000633:toxicity*; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D014475:Uncoupling Agents / Q000633:toxicity*
chemical_list: D000090:Acetoacetates; D007659:Ketones; D014475:Uncoupling Agents; D012402:Rotenone; C016635:acetoacetic acid; D042967:Electron Transport Complex I; D020155:3-Hydroxybutyric Acid