Microglia Promote the Death of Developing Purkinje Cells

Abstract

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.

Macrophage and microglia ontogeny in the mouse visual system can be traced by the expression of Cathepsins B and D

“…Therefore, phagocytic cells labeled in the developing optic nerve may be participating in the clearance of axonal debris of degenerating ganglion cells, as has been proposed for microglia in the postnatal rabbit retina (Schnitzer, 1989) or for activated microglia after optic nerve cut (Thanos et al, 1992;Lawson et al, 1994). Furthermore, during development of other regions of the murine central nervous system, apoptotic neurons and their connections are actively and rapidly removed by microglia (Frade and Barde, 1998;Marin-Teva et al, 2004).…”

The ecology of brain tumors: lessons learned from neurofibromatosis-1

“…Tumor-associated microglia constitute the main population of brain immune cells (Graeber et al, 2002) and are important for monitoring their local environment, regulating function and apoptosis, and secreting proinflammatory cytokines (Banati et al, 1993;Elkabes et al, 1996;Marı´n-Teva et al, 2004;Roumier et al, 2004). These resident brain immune system mononuclear cells can be recruited by glioma tumors cells to the local tumor microenvironment by vascular Figure 3 Co-evolution of neoplastic and non-neoplastic cells in gliomas.…”

Rorα, a pivotal nuclear receptor for Purkinje neuron survival and differentiation: From development to ageing

“…However, further studies will be needed to determine whether the observed Purkinje cell loss is linked to an increased ROS production in Rora +/sg mutants. Furthermore, many studies have proposed the existence of a developmental Purkinje cell death period, occurring around P3 (52)(53)(54)(55)(56). Interestingly, in Rora sg/sg mice, Purkinje cell loss seems to occur during this period (32).…”