Nakajima Shingo, Numakawa Tadahiro, Adachi Naoki, Yoon Hyung Shin, Odaka Haruki, Ooshima Yoshiko, Kunugi Hiroshi
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan; Faculty of Health Science, Hokkaido University, Sapporo, Japan.
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan; Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Neurosci Lett. 2016 Mar 11;616:105-10. doi: 10.1016/j.neulet.2016.01.052. Epub 2016 Jan 28.
Glucagon-like peptide-1 (GLP-1), an insulinotropic peptide secreted from enteroendocrine cells, has been known to have a neuroprotective effect. However, it is not fully understood the intracellular mediator of GLP-1 signaling in neuronal cells. In the present study, we examined the change in intracellular signaling of cortical neurons after GLP-1 application and luminal glucose stimulation in vitro and in vivo. GLP-1 receptor was highly expressed in cultured cortical neurons and brain tissues including the prefrontal cortex and hippocampus. The activation of GLP-1 receptor (5min) significantly decreased levels of phosphorylated extracellular signal-regulated kinase (pERK), which is involved in neuronal cell survival and death, in cultured cortical neurons. Oral glucose administration also rapidly reduced pERK levels in the prefrontal cortex, while intraperitoneal glucose injection did not show such an effect. Further, GLP-1 attenuated hydrogen peroxide-induced cell death and hyperactivity of ERK in cultured cortical neurons. It is possible that increased GLP-1 by luminal glucose stimulation affects cortical system including the maintenance of neuronal cell survival.
胰高血糖素样肽-1（GLP-1）是一种由肠内分泌细胞分泌的促胰岛素肽，已知具有神经保护作用。然而，神经元细胞中GLP-1信号传导的细胞内介质尚未完全明确。在本研究中，我们在体外和体内检测了应用GLP-1和管腔葡萄糖刺激后皮质神经元细胞内信号的变化。GLP-1受体在培养的皮质神经元以及包括前额叶皮质和海马体在内的脑组织中高表达。在培养的皮质神经元中，GLP-1受体激活（5分钟）显著降低了参与神经元细胞存活和死亡的磷酸化细胞外信号调节激酶（pERK）的水平。口服葡萄糖也能迅速降低前额叶皮质中的pERK水平，而腹腔注射葡萄糖则未显示出这种效果。此外，GLP-1可减轻过氧化氢诱导的培养皮质神经元细胞死亡和ERK过度激活。管腔葡萄糖刺激导致的GLP-1增加可能会影响包括维持神经元细胞存活在内的皮质系统。
