Astrocytes are known to regulate cerebral blood flow and are thought to release angiogenic factors. Given their high metabolic demands, oligodendrocytes and Schwann cells have a vested interest in regulating blood flow and having access

to oxygen, glucose, and substrates for lipogenesis and proteolipid construction of myelin sheaths. Indeed, it is interesting to note that myelination is a largely postnatal Dolutegravir ic50 process in the mammalian brain, a time frame distinguished by high oxygen tension compared with in utero conditions, and that postnatal hypoxia can delay developmental myelination in animal models. Might an oxygen-regulated trigger coordinate with activity-dependent inductive signals to time the onset of myelination? Oligodendrocyte cell-cell interactions with blood vessels and axons they invest represent fruitful areas for future research. It is not surprising that evolutionary progression is coupled to new glial subtypes with specialized functions in the CNS. Simple organisms like Drosophila have glial subtypes that act as nonprofessional phagocytes and respond

to injury. The molecular mechanisms that drive these events, for example, the glial-expressed engulfment receptor Draper, are conserved in mammalian glia ( Scheib et al., 2012 and Wu et al., 2009). But the appearance of microglia Cilengitide mouse added a new dimension to brain health. Responses to neuronal death or injury by these professional phagocytes are far more efficient than those of astrocytes, and microglia, as proper immune cells, also regulate inflammation, cytotoxicity, and antigen presentation. Perhaps unexpectedly, because they are thought of as mainly immune cells, microglia were recently shown to regulate the refinement of developing Suplatast tosilate neural circuits through removal of exuberant synaptic connections. At the moment, there is little evidence for functional heterogeneity in glial subclasses in simple organisms like Drosophila and C. elegans. In flies, perhaps all astrocytes are the same.

However, the long evolutionary relationship between astroglia and neurons predicts a higher degree of astrocyte heterogeneity in vertebrates. Specialized vertebrate neuron subtypes generated through neural tube patterning and increased regionality and complexity of the CNS might have demanded diversified glial solutions that would have been coselected for over time. So, what is the evidence for astrocyte heterogeneity? Many studies have shown that astrocytes display morphological differences in white versus gray matter and in different brain regions. More recently, expression profiling has indicated that cells expressing the astrocyte marker Aldh1L1-GFP, or that encode TRAPP to label polysomal RNA, are regionally heterogeneous at the molecular level ( Cahoy et al., 2008, Doyle et al., 2008 and Heiman et al., 2008).