Glucagon-like peptide-2 rescues memory impairments and neuropathological changes in a mouse model of dementia induced by the intracerebroventricular administration of streptozotocin
Glucagon-like peptide-2 rescues memory impairments and neuropathological changes in a mouse model of dementia induced by the intracerebroventricular administration of streptozotocin
复制标题
胰高血糖素样肽 2 可挽救脑室内注射链脲佐菌素诱发的痴呆小鼠模型的记忆障碍和神经病理学变化
作者：
S. Sasaki‐Hamada;Masaatsu Ikeda;J. Oka
胰高血糖素样肽2(GLP-2)是由肠、胰腺和脑中表达的胰高血糖素原基因衍生而来。我们先前的研究表明，GLP-2改善了内毒素诱导的记忆损伤。本研究旨在进一步探讨GLP-2在脑室注射链脲佐菌素(ICV-STZ)所致小鼠记忆障碍中的作用。每隔一天(第一天和第三天)给药，以诱导雄性ddy小鼠痴呆。脑室注射GLP-2(0.6μg/只，icv)，连续给药5天。在这些小鼠中，我们检测了空间工作记忆，即氧化应激或神经发生的生化参数。GLP-2治疗恢复了ICV-STZ治疗的小鼠的空间工作记忆。ICV-STZ组小鼠血中硫代巴比妥酸活性物质(TBARS)显著升高，谷胱甘肽(GSH)水平显著降低，GLP-2可显著恢复ICV-STZ所致的上述变化。GLP-2还显著恢复了ICV-STZ治疗小鼠齿状回颗粒下区的神经再生。在此，我们证明了GLP-2显著恢复了ICV-STZ诱导的记忆损伤以及生化和组织病理学改变，因此，我们认为GLP-2的记忆恢复能力是由于其降低氧化应激的潜力所致。
Glucagon-like peptide 2 (GLP-2) is derived from the proglucagon gene expressed in the intestines, pancreas and brain. Our previous study showed that GLP-2 improved lipopolysaccharide-induced memory impairments. The current study was designed to further investigated the potential of GLP-2 in memory impairment induced by intracerebroventricular administration of streptozotocin (ICV-STZ) in mice, which have been used as an animal model of sporadic Alzheimer’s disease (AD). STZ was administered on alternate days (Day-1 and Day-3) in order to induce dementia in male ddY mice. ICV-STZ-treated mice were administered GLP-2 (0.6 μg/mouse, ICV) for 5 days from 14 days after the first ICV administration of STZ. In these mice, we examined spatial working memory, the biochemical parameters of oxidative stress, or neurogenesis. The GLP-2 treatment restored spatial working memory in ICV-STZ-treated mice. ICV-STZ-treated mice showed markedly increased thiobarbituric acid reactive species (TBARS) and decreased glutathione (GSH) levels, and GLP-2 significantly restored these ICV-STZ-induced changes. GLP-2 also significantly restored neurogenesis in the subgranular zone of the dentate gyrus in ICV-STZ-treated mice. We herein demonstrated that GLP-2 significantly restored ICV-STZ-induced memory impairments as well as biochemical and histopathological alterations, and accordingly, propose that the memory restorative ability of GLP-2 is due to its potential to reduce oxidative stress.