Metformin (Met) is a first-line drug for type 2 diabetes mellitus (T2DM). Numerous studies have shown that Met exerts beneficial effects on a variety of neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). However, it is still largely unclear how Met acts on neurons. Here, by treating acute hippocampal slices with Met (1 μM and 10 μM) and recording synaptic transmission as well as neuronal excitability of CA1 pyramidal neurons, we found that Met treatments significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs), but not amplitude. Neither frequency nor amplitude of miniature inhibitory postsynaptic currents (mIPSCs) were changed with Met treatments. Analysis of paired-pulse ratios (PPR) demonstrates that enhanced presynaptic glutamate release from terminals innervating CA1 hippocampal pyramidal neurons, while excitability of CA1 pyramidal neurons was not altered. Our results suggest that Met preferentially increases glutamatergic rather than GABAergic transmission in hippocampal CA1, providing a new insight on how Met acts on neurons.

中文翻译：

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二甲双胍增强兴奋性突触传递到海马CA1锥体神经元上。

二甲双胍（Met）是治疗2型糖尿病（T2DM）的一线药物。大量研究表明，Met对多种神经系统疾病具有有益作用，包括阿尔茨海默氏病（AD），帕金森氏病（PD）和亨廷顿氏病（HD）。但是，目前仍不清楚Met如何作用于神经元。在这里，通过用Met（1μM和10μM）处理急性海马切片并记录突触传递以及CA1锥体神经元的神经元兴奋性，我们发现Met治疗显着增加了小型兴奋性突触后突触电流（mEPSCs）的频率振幅。Met处理并没有改变微型抑制性突触后电流（mIPSCs）的频率和幅度。配对脉冲比（PPR）分析表明，神经末梢释放CA1海马锥体神经元的突触前谷氨酸释放增强，而CA1锥体神经元的兴奋性没有改变。我们的结果表明，Met优先增加海马CA1中的谷氨酸能而非GABA能传递，为Met如何作用于神经元提供了新的见解。