Acute Exposure to the Mitochondrial Complex I Toxin Rotenone Impairs Synaptic Long-Term Potentiation in Rat Hippocampal Slices

作者：Kimura Ryoichi; Ma Lu Yao; Wu Chen; Turner Dharshaun; Shen Jian Xin; Ellsworth Kevin; Wakui Makoto; Maalouf Marwan; Wu Jie^*

来源：CNS Neuroscience & Therapeutics, 2012, 18(8): 641-646.

DOI：10.1111/j.1755-5949.2012.00337.x

• Hippocampal slice
• Ketone
• Long-term potentiation
• Mitochondrial dysfunction
• Rotenone

Aims: 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 x 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 CA3CA1 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 beta-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.

• 出版日期2012
• 单位汕头大学