Ischemic Preconditioning Mediates Neuroprotection against Ischemia in Mouse Hippocampal CA1 Neurons by Inducing Autophagy.
Ischemic Preconditioning Mediates Neuroprotection against Ischemia in Mouse Hippocampal CA1 Neurons by Inducing Autophagy.
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DOI：
10.1371/journal.pone.0137146
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Gao C;Cai Y;Zhang X;Huang H;Wang J;Wang Y;Tong X;Wang J;Wu J
海马 CA1 区对缺氧和缺血性损伤敏感，但可以通过缺血预适应 (IPC) 进行保护。然而，IPC保护海马CA1神经元的机制仍在研究中。此外，自噬在决定海马神经元命运中的作用尚不清楚。在这里，我们在氧糖剥夺 (OGD) 和双侧颈动脉闭塞 (BCCAO) 模型中检查了 IPC 是否诱导自噬来减轻体外和体内海马 CA1 神经元死亡。海马神经元的存活率从非 IPC 组（55 分钟 OGD）的 51.5% ± 6.3% 增加到 IPC 组（15 分钟 OGD，24 小时后 55 分钟 OGD）的 77.3% ± 7.9%。海马 CA1 层神经元数量从非 IPC 组（20 分钟 BCCAO）的 182 ± 26 个细胞/mm2 增加到 IPC 组（1 分钟×3 BCCAO，24 小时后 20 分钟 BCCAO）的 278 ± 55 个细胞/mm2。预处理组中 Akt 磷酸化和微管相关蛋白轻链 3 (LC3)-II/LC3-I 表达增加。而且，IPC的保护作用只能通过抑制自噬活性而消除，而不能通过体外阻断Akt的激活来消除。通过体内实验，我们发现预处理组中 LC3 表达上调，同时海马 CA1 神经元的神经元存活率增加。 IPC 对海马 CA1 神经元的神经保护作用被 3-MA 处理完全抑制。相比之下，海马 CA3 神经元没有表现出自噬活性的变化或 IPC 的有益作用。这些数据表明，IPC 可能通过诱导 Akt 独立的自噬来减轻海马 CA1 神经元的缺血性损伤。
The hippocampal CA1 region is sensitive to hypoxic and ischemic injury but can be protected by ischemic preconditioning (IPC). However, the mechanism through which IPC protects hippocampal CA1 neurons is still under investigation. Additionally, the role of autophagy in determining the fate of hippocampal neurons is unclear. Here, we examined whether IPC induced autophagy to alleviate hippocampal CA1 neuronal death in vitro and in vivo with oxygen glucose deprivation (OGD) and bilateral carotid artery occlusion (BCCAO) models. Survival of hippocampal neurons increased from 51.5% ± 6.3% in the non-IPC group (55 min of OGD) to 77.3% ± 7.9% in the IPC group (15 min of OGD, followed by 55 min of OGD 24 h later). The number of hippocampal CA1 layer neurons increased from 182 ± 26 cells/mm2 in the non-IPC group (20 min of BCCAO) to 278 ± 55 cells/mm2 in the IPC group (1 min × 3 BCCAO, followed by 20 min of BCCAO 24 h later). Akt phosphorylation and microtubule-associated protein light chain 3 (LC3)-II/LC3-I expression were increased in the preconditioning group. Moreover, the protective effects of IPC were abolished only by inhibiting the activity of autophagy, but not by blocking the activation of Akt in vitro. Using in vivo experiments, we found that LC3 expression was upregulated, accompanied by an increase in neuronal survival in hippocampal CA1 neurons in the preconditioning group. The neuroprotective effects of IPC on hippocampal CA1 neurons were completely inhibited by treatment with 3-MA. In contrast, hippocampal CA3 neurons did not show changes in autophagic activity or beneficial effects of IPC. These data suggested that IPC may attenuate ischemic injury in hippocampal CA1 neurons through induction of Akt-independent autophagy.