Koriyama Yoshiki, Homma Keiko, Kato Satoru
Saturo Kato, Department of Molecular Neurobiology, Graduate School of Medicine, University of Kanazawa, 13-1 Takara-machi, Kanazawa 920-8640, Japan.
Adv Exp Med Biol. 2006;572:333-7. doi: 10.1007/0-387-32442-9_47.
Generally, nerve injury of adult mammalian CNS neurons leads to a retrograde neuronal degeneration and cell death. The retinal ganglion cells (RGCs) of rat fail to regenerate and become apoptotic after optic nerve injury. In contrast, goldfish RGCs can survive and regrow their axons after injury. Focusing on this different response of RGCs in both species to optic nerve injury, we compared cell death and cell survival signals in the rat and goldfish RGCs after optic nerve injury. In goldfish retina, levels of phospho-Akt (p-Akt) and phospho-Bad (p-Bad) first rapidly increased at 3-5 days after optic nerve injury. Subsequently, levels of Bcl-2 increased and caspase-3 activity decreased at 10 days after nerve injury. In rat retina, levels of p-Akt and p-Bad first rapidly decreased at 1-2 days after optic nerve injury. Subsequently, levels of Bax and caspase-3 activity increased 6 days after optic nerve crush. These changes after optic nerve injury were all morphologically localized only in the RGCs. The data suggest that goldfish RGCs are warranted the cell survival by rapid p-Akt and subsequent Bcl-2 activations during the optic nerve regeneration, whereas rat RGCs are made a progress of the cell death by rapid inactivation of p-Akt and subsequent activation of Bax after optic nerve crush.
一般来说，成年哺乳动物中枢神经系统神经元的神经损伤会导致逆行性神经元变性和细胞死亡。大鼠的视网膜神经节细胞（RGCs）在视神经损伤后无法再生并发生凋亡。相比之下，金鱼的RGCs在损伤后能够存活并使其轴突再生。针对这两个物种的RGCs对视神经损伤的不同反应，我们比较了视神经损伤后大鼠和金鱼RGCs中的细胞死亡和细胞存活信号。在金鱼视网膜中，视神经损伤后3 - 5天，磷酸化Akt（p - Akt）和磷酸化Bad（p - Bad）水平首先迅速升高。随后，神经损伤后10天，Bcl - 2水平升高，caspase - 3活性降低。在大鼠视网膜中，视神经损伤后1 - 2天，p - Akt和p - Bad水平首先迅速下降。随后，视神经挤压后6天，Bax水平和caspase - 3活性升高。视神经损伤后的这些变化在形态学上仅局限于RGCs。数据表明，在视神经再生过程中，金鱼RGCs通过快速激活p - Akt和随后激活Bcl - 2来保证细胞存活，而大鼠RGCs在视神经挤压后通过p - Akt的快速失活和随后Bax的激活而走向细胞死亡。
