Microglia promote the death of developing Purkinje cells.
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.
Biologie des Interactions Neurone-glie, INSERM U.495, IFR 70, UPMC, 47 Bd de l'hôpital, 75013 Paris, France.
José Luis
JL
Marín-Teva
Isabelle
I
Dusart
Catherine
C
Colin
Annie
A
Gervais
Nico
N
van Rooijen
Michel
M
Mallat
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002525:Cerebellar Cortex / Q000166:cytology / Q000254:growth & development*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology; D011689:Purkinje Cells / Q000166:cytology / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D000906:Antibodies; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D018124:Receptors, Tumor Necrosis Factor; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases