Shibasaki Koji, Hosoi Nobutake, Kaneko Ryosuke, Tominaga Makoto, Yamada Katsuya
Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Division of Cell Signaling, National Institute for Physiological Sciences, Okazaki, Japan.
J Neurochem. 2017 Feb;140(3):395-403. doi: 10.1111/jnc.13741. Epub 2016 Aug 9.
It was previously reported that functional glycine receptors were expressed in neonatal prefrontal cortex; however, the glycine-releasing cells were unknown. We hypothesized that astrocytes might be a major glycine source, and examined the glycine release properties of astrocytes. We also hypothesized that dopamine (DA) might be a trigger for the astrocytic glycine release, as numerous DA terminals localize in the cortex. We combined two different methods to confirm the glycine release from astrocytes. Firstly, we analyzed the supernatant of astrocytes by amino acid analyzer after DA stimulation, and detect significant glycine peak. Furthermore, we utilized a patch-clamp biosensor method to confirm the glycine release from astrocytes by using GlyRα1 and Glyβ-expressing HEK293T cells, and detected significant glycine-evoked current upon DA stimulation. Thus, we clearly demonstrated that DA induces glycine release from astrocytes. Surprisingly, DA caused a functional reversal of astrocytic glycine transporter 1, an astrocytic type of glycine transporter, causing astrocytes to release glycine. Hence, astrocytes transduce pre-synaptic DA signals to glycine signals through a reversal of astrocytic glycine transporter 1 to regulate neuronal excitability. Cover Image for this issue: doi: 10.1111/jnc.13785.
此前有报道称，功能性甘氨酸受体在新生大鼠前额叶皮层中表达；然而，释放甘氨酸的细胞尚不清楚。我们推测星形胶质细胞可能是主要的甘氨酸来源，并研究了星形胶质细胞的甘氨酸释放特性。我们还推测多巴胺（DA）可能是星形胶质细胞释放甘氨酸的触发因素，因为大量的DA终末定位于皮层。我们结合了两种不同的方法来证实星形胶质细胞释放甘氨酸。首先，我们在DA刺激后通过氨基酸分析仪分析星形胶质细胞的上清液，并检测到显著的甘氨酸峰。此外，我们利用膜片钳生物传感器方法，通过使用表达GlyRα1和Glyβ的HEK293T细胞来证实星形胶质细胞释放甘氨酸，并在DA刺激时检测到显著的甘氨酸诱发电流。因此，我们清楚地证明了DA诱导星形胶质细胞释放甘氨酸。令人惊讶的是，DA导致星形胶质细胞甘氨酸转运体1（一种星形胶质细胞类型的甘氨酸转运体）功能逆转，使星形胶质细胞释放甘氨酸。因此，星形胶质细胞通过星形胶质细胞甘氨酸转运体1的逆转将突触前DA信号转化为甘氨酸信号，以调节神经元兴奋性。本期封面图片：doi:10.1111/jnc.13785 。
