Yoon Dae-Kun, Hwang In Koo, Yoo Ki-Yeon, Lee Yoon-Bok, Lee Jae-Jung, Kim Jong-Hyun, Kang Tae-Cheon, Lee Bong-Hee, Sohn Heon-Soo, Won Moo Ho
Department of Surgery, College of Medicine, Hallym University, Chuncheon 200-702, South Korea.
Neurosci Res. 2006 Aug;55(4):434-41. doi: 10.1016/j.neures.2006.04.014. Epub 2006 Jun 6.
In this study, we examined changes in the level and immunoreactivity of alpha-synuclein in the hippocampal CA1 region of adult (6 months old) and aged (24 months old) gerbils after 5 min of transient forebrain ischemia. The delayed neuronal death of CA1 pyramidal cells in adult gerbils was severer than that in aged gerbils 4 days after ischemia/reperfusion. Alpha-synuclein immunoreactivity in the CA1 region of adult and aged gerbils significantly changed after ischemia. In control animals, alpha-synuclein immunoreactivity and level in the aged-gerbil CA1 region were higher than those in the adult-gerbil CA1 region. In both adult and aged gerbils, alpha-synuclein immunoreactivity and level started to increase 3h after ischemia, and they were highest 1 day after ischemia. Thereafter, alpha-synuclein immunoreactivity and level decreased with time after ischemia. We also observed the effects of Cu,Zn-superoxide dismutase (SOD1) on ischemic damage using the Pep-1 transduction domain. Alpha-synuclein level in the CA1 region was lower in Pep-1-SOD1-treated adult and aged gerbils than in vehicle-treated adult and aged gerbils. We conclude that neuronal loss in the hippocampal CA1 region of adult gerbils was more prominent than that in aged gerbils 4 days after ischemia/reperfusion. The higher level of alpha-synuclein in the aged-gerbil CA1 region than that in the adult-gerbil CA1 region may be associated with the earlier induction of reactive oxygen species, and Pep-1-SOD1 potentially and reversibly inhibits the accumulation of alpha-synuclein in the CA1 region after transient ischemia.
在本研究中，我们检测了成年（6个月大）和老年（24个月大）沙鼠在前脑短暂缺血5分钟后，海马CA1区α-突触核蛋白水平及免疫反应性的变化。缺血/再灌注4天后，成年沙鼠CA1锥体细胞的延迟性神经元死亡比老年沙鼠更严重。成年和老年沙鼠缺血后，CA1区α-突触核蛋白免疫反应性显著改变。在对照动物中，老年沙鼠CA1区的α-突触核蛋白免疫反应性和水平高于成年沙鼠CA1区。在成年和老年沙鼠中，α-突触核蛋白免疫反应性和水平在缺血后3小时开始升高，在缺血后1天达到最高。此后，缺血后α-突触核蛋白免疫反应性和水平随时间下降。我们还使用Pep-1转导结构域观察了铜锌超氧化物歧化酶（SOD1）对缺血损伤的影响。Pep-1-SOD1处理的成年和老年沙鼠CA1区的α-突触核蛋白水平低于载体处理的成年和老年沙鼠。我们得出结论，缺血/再灌注4天后，成年沙鼠海马CA1区的神经元丢失比老年沙鼠更明显。老年沙鼠CA1区α-突触核蛋白水平高于成年沙鼠CA1区，这可能与活性氧的早期诱导有关，并且Pep-1-SOD1可能可逆地抑制短暂缺血后CA1区α-突触核蛋白的积累。
