Development of microglia in the chick embryo spinal cord: Implications in the regulation of motoneuronal survival and death

Abstract

The role of microglia during normal development of the nervous system is still not well understood. In the present study, a chick embryo model was used to examine the development of microglia in the spinal cord and characterize their changes in response to naturally occurring and pathological death of motoneurons (MNs). The microglial response to MN axotomy and the effects of microglial activation on MN survival were also studied. We found that: 1) macrophages/microglial cells were present in the spinal cord at early developmental stages (E3) and that they were recruited after normal and induced MN apoptosis; 2) although many microglial cells were seen phagocytosing apoptotic bodies, a proportion of dying cells were devoid of engulfing microglia; 3) axotomy of mature MNs was accompanied by microglial activation in the absence of MN death; 4) excitotoxic (necrotic) MN death provoked a rapid and massive microglial recruitment with phagocytic activity; 5) lipopolysaccharide-induced microglial activation in vivo resulted in the death of immature, but not mature, microglia; and 6) overactivation of microglia modulated the survival of mature MNs, either by killing them or by enhancing their vulnerability to die in response to a mild injury. Taken together, these observations indicate that normal microglia do not play an active role in triggering apoptosis of developing MNs. Rather, they act as phagocytes for the removal of dying cells during the process of programmed cell death.

Pattern of invasion of the embryonic mouse spinal cord by microglial cells at the time of the onset of functional neuronal networks

“…Some microglial cell precursors are observed in the lumen of the CC even at early developmental stages and in the VZ occurs at E10.5, suggesting that microglial cells use the CC as a route of migration toward the VZ, as previously suggested in the chick embryo (Caldero et al, 2009). Microglial cells in the VZ are actively proliferating, which could also account for the developmental increase in microglial cell number in the gray matter after E12.5.…”

“…Although there is evidence that interactions can take place between dying neurons and microglial cells in the spinal cord of rat and mouse embryos (Sedel et al, 2004) or of chick embryos (Caldero et al, 2009), the activation states of microglial cells during early embryonic spinal cord development are still poorly documented. Interestingly, microglial cells accumulating in the LMC at E13.5 have an amoeboid morphology with several endosomelike compartments (Fig.…”

“…More recently, it has been proposed that microglial cells surrounding the embryonic rat spinal cord at E12.5-E13.5 instruct motoneurons to become competent to die, rather than actively triggering their apoptosis (Sedel et al, 2004). However, in the chick embryo, microglial cells begin to invade the spinal cord parenchyma at E7 [corresponding to E14.5 in the mouse embryo and to E15.5 in the rat embryo (Bulter and Juurlink, 1987;Kaufman and Bard, 1999)], after the peak of naturally occurring developmental cell death (DCD) of motoneurons, suggesting that microglial cells could have a macrophagelike function only (Caldero et al, 2009).…”

Inflammation in Alzheimer Disease--A Brief Review of the Basic Science and Clinical Literature

“…Migration of blood-derived macrophages into the CNS has also been suggested to occur later in fetal development (reviewed in Chan et al 2007). Throughout development, microglia may play an important role in remodeling of the brain by removing presumably redundant, apoptotic neurons (Bessis et al 2007;Caldero et al 2009). In vivo activity of microglia has recently been visualized using two photon microscopy techniques (Davalos et al 2005;Nimmerjahn et al 2005;Wake et al 2009).…”

Cellules microgliales et développement du système nerveux central chez l’embryon

“…Après E15,5, toutes les cellules microgliales sont ramifiées et réparties de façon homogène dans le parenchyme spinal. Un processus de colonisation analogue a été observé chez l'embryon de poulet [12]. Ce processus d'invasion peut être modulé par le microenvironnement.…”