Molecular mechanisms of autophagic neuron death

出生时缺氧/缺血（H/I）脑损伤是导致脑瘫、智力低下和癫痫的重要原因。H/I损伤还会引起能量衰竭、氧化应激和离子通量不平衡，导致脑神经元自噬的高度诱导。H/I损伤后神经元自噬的诱导通常被认为是神经保护作用，因为它能维持细胞内稳态。然而，我们最近的研究结果表明，新生儿H/I损伤后海马锥体神经元的细胞死亡在很大程度上是由Atg7缺乏预防的。这是我们所知的第一个为新生儿小鼠H/I脑损伤后自噬诱导神经元死亡提供直接证据的报告，使用的小鼠不能在中枢神经系统组织中特异性地进行自噬。因此，抑制自噬诱导的神经元死亡的治疗策略可能对儿童和成人H/I脑损伤的治疗有益。

Hypoxia/ischemia (H/I) brain injury at birth is an important cause of cerebral palsy, mental retardation, and epilepsy. The H/I insult also causes energy failure, oxidative stress, and unbalanced ion fluxes, leading to high induction of autopahgy in brain neurons. Induction of neuronal autophagy after H/I injury is generally considered neuroprotective, as it maintains cellular homeostasis. However, our recent results show that cell death of hippocampal pyramidal neurons following neonatal H/I injury is largely prevented by Atg7 deficiency. This is the first report that we are aware of providing direct evidence for autophagy-induced neuron death after neonatal mouse H/I brain injury, using mice that cannot execute autophagy specifically in CNS tissue. Thus, therapeutic strategies to inhibit autophagy-induced neuron death may prove beneficial in the treatment of both pediatric and adult H/I brain injury.