Marín-Teva José Luis, Dusart Isabelle, Colin Catherine, Gervais Annie, van Rooijen Nico, Mallat Michel
Biologie des Interactions Neurone-glie, INSERM U.495, IFR 70, UPMC, 47 Bd de l'hôpital, 75013 Paris, France.
Neuron. 2004 Feb 19;41(4):535-47. doi: 10.1016/s0896-6273(04)00069-8.
The loss of neuronal cells, a prominent event in the development of the nervous system, involves regulated triggering of programmed cell death, followed by efficient removal of cell corpses. Professional phagocytes, such as microglia, contribute to the elimination of dead cells. Here we provide evidence that, in addition to their phagocytic activity, microglia promote the death of developing neurons engaged in synaptogenesis. In the developing mouse cerebellum, Purkinje cells die, and 60% of these neurons that already expressed activated caspase-3 were engulfed or contacted by spreading processes emitted by microglial cells. Apoptosis of Purkinje cells in cerebellar slices was strongly reduced by selective elimination of microglia. Superoxide ions produced by microglial respiratory bursts played a major role in this Purkinje cell death. Our study illustrates a mammalian form of engulfment-promoted cell death that links the execution of neuron death to the scavenging of dead cells.
神经元细胞的丧失是神经系统发育过程中的一个突出事件，涉及程序性细胞死亡的调控触发，随后是细胞尸体的有效清除。专业吞噬细胞，如小胶质细胞，有助于清除死细胞。在这里，我们提供证据表明，除了吞噬活性外，小胶质细胞还促进参与突触形成的发育中神经元的死亡。在发育中的小鼠小脑中，浦肯野细胞死亡，这些已经表达活化半胱天冬酶-3的神经元中有60%被小胶质细胞发出的伸展过程吞噬或接触。通过选择性消除小胶质细胞，小脑切片中浦肯野细胞的凋亡显著减少。小胶质细胞呼吸爆发产生的超氧离子在这种浦肯野细胞死亡中起主要作用。我们的研究阐明了一种哺乳动物形式的吞噬促进性细胞死亡，它将神经元死亡的执行与死细胞的清除联系起来。
