Early induction of neuronal lipocalin-type prostaglandin D synthase after hypoxic-ischemic injury in developing brains
Early induction of neuronal lipocalin-type prostaglandin D synthase after hypoxic-ischemic injury in developing brains
复制标题
DOI：
10.1016/j.neulet.2007.04.016
复制
发表时间：
2007-06
影响因子：
2.5
通讯作者：
Hidetoshi Taniguchi;I. Mohri;Hitomi Okabe-Arahori;T. Kanekiyo;Kuriko Kagitani-Shimono;Kazuko Wada;Y. Urade;M. Nakayama;K. Ozono;M. Taniike
中科院分区：
文献类型：
--
作者：
Hidetoshi Taniguchi;I. Mohri;Hitomi Okabe-Arahori;T. Kanekiyo;Kuriko Kagitani-Shimono;Kazuko Wada;Y. Urade;M. Nakayama;K. Ozono;M. Taniike
Lipocalin-type prostaglandin（PG）D synthase（L-PGDS）在遗传性神经系统疾病（包括球样细胞脑白质营养不良（twitcher）和GM 1和GM 2神经节苷脂沉积症）的小鼠模型中的少突胶质细胞（OL）中以及多发性硬化症患者的脑中上调。由于L-PGDS缺陷的抽搐小鼠经历广泛的神经元死亡，我们得出结论，L-PGDS功能保护神经元变性。在这项研究中，我们调查了L-PGDS是否也在新生儿缺氧缺血性脑病（HIE）引起的急性和大面积脑损伤中上调。对死于缺氧缺血性脑病的新生儿大脑的分析表明，在梗死灶中存活的神经元表达L-PGDS。在出生后第7天（PND）制作新生儿HIE小鼠模型。在该模型中，在复氧后24小时，同侧半球的整体梗死是明显的。复氧后10分钟，在皮质明显正常的神经元中以及此后在梗死区邻近的神经元中已经观察到强烈的L-PGDS免疫反应性。定量RT-PCR结果显示，再给氧后1h，脑梗死侧L-PGDS mRNA表达水平是假手术侧的33倍，24 h后降至正常水平。此外，在人类和小鼠大脑中，许多L-PGDS阳性细胞也对p53具有免疫反应性;其中一些表达裂解的caspase-3。L-PGDS在退化神经元中的表达意味着L-PGDS作为早期应激蛋白发挥作用，以防止HIE大脑中的神经元死亡。
Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is up-regulated in oligodendrocytes (OLs) in mouse models for genetic neurological disorders including globoid cell leukodystrophy (twitcher) and GM1and GM2gangliosidoses and in the brain of patients with multiple sclerosis. Since L-PGDS-deficient twitcher mice undergo extensive neuronal death, we concluded that L-PGDS functions protectively against neuronal degeneration. In this study, we investigated whether L-PGDS is also up-regulated in acute and massive brain injury resulting from neonatal hypoxic-ischemic encephalopathy (HIE). Analysis of brains from human neonates who had died from HIE disclosed that the surviving neurons in the infarcted lesions expressed L-PGDS. Mouse models for neonatal HIE were made on postnatal day (PND) 7. Global infarction in the ipsilateral hemisphere was evident at 24h after reoxygenation in this model. Intense L-PGDS immunoreactivity was already observed at 10min after reoxygenation in apparently normal neurons in the cortex, and thereafter, in neurons adjacent to the infarcted area. Quantitative RT-PCR revealed that the L-PGDS mRNA level of the infarcted hemisphere was 33-fold higher than that of the sham-operated mouse brains at 1h after reoxygenation and that it decreased to the normal level by 24h thereafter. Furthermore, in both human and mouse brains, many of L-PGDS-positive cells were also immunoreactive for p53; and some of these expressed cleaved caspase-3. The expression of L-PGDS in degenerating neurons implies that L-PGDS functions as an early stress protein to protect against neuronal death in the HIE brain.