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Abstract

Brain lesions, even of the most subtle type, are accompanied by the activation of microglia, the main immune cells of the brain. Microglial cells dramatically increase in number through proliferation and adhere to the injured neurons, where they displace the synaptic input. After proliferation, microglia gradually migrate into the nearby parenchyma and appear to decrease in number. Here we examined the possible involvement of apoptosis in the regulation of the microglial cell number using Terminal transferase mediated d-UTP Nick End-Labelling (TUNEL). In vitro, cell death is a common phenomenon in microglial cell cultures, and is enhanced by the withdrawal of the mitogen, granulocyte-macrophage colony stimulating factor. In vivo, application of the TUNEL-reaction revealed TUNEL-positive microglia beginning at day 4, with a peak 7 days after transection of the facial nerve. Surprisingly, TUNEL-labelling in vivo was localized on the outer side of the nuclear membrane and in the microglial cytoplasm, with very little staining within the nucleus itself. These TUNEL-labelled cells also lacked other classic morphological signs of apoptosis, like membrane blebbing, chromatin condensation and apoptotic bodies. These data suggest that the regulation of post-mitotic microglia is not mediated by the classic pathway of apoptosis.

Proinflammatory cytokine regulation of cyclic AMP‐phosphodiesterase 4 signaling in microglia in vitro and following CNS injury

“…In this paradigm PDE4B was constitutively localized to the nucleus. Although cytokine stimulation of microglia often leads to their apoptosis (Jones et al, 1997), it is yet to be determined what is the role of the transient nuclear translocation of PDE4B from the cytoplasm in activated microglia in the current study and whether such translocation involves either a cyclic AMP hydrolytic function of PDE4B in the nucleus or whether PDE4B participates as a scaffolding molecule with other signaling intermediaries. Through the use of PredictNLS we have shown that PDE4B2 may contain a putative [DE]RxKKKK NLS sequence, which was highly conserved among species.…”

The Yin and Yang of Microglia

“…Additionally, it has recently been shown that microglia are able to cross-present exogenous antigens on MHC I to CD8+ T cells [61]. In the course of recovery from injury, activated microglia can be eliminated by apoptosis [54,62]. Not only neurons, but also astrocytes can be critical for microglial activation, e.g.…”

Androgens suppress antigen-specific T cell responses and IFN-γ production during intracranial LCMV infection

“…LCMV infection between males and females, removal of endogenous androgens in males via orchidectomy decreased the number of CD45 int cells compared to sham-operated males, and addition of exogenous androgens to female mice via DHT pellet implantation increased the number of CD45 int cells compared to control females. Microglia are able to undergo proliferation and apoptosis in response to various stimuli (Jones et al, 1997; Remington et al, 2007; Wirenfeldt et al, 2007), but little is known about the effects of sex hormones on these processes in microglia. Possible roles of physiologic levels of estrogens on microglial survival/proliferation and the balance of estrogens’ effects with the effects of androgens must also be considered.…”