Finally, astrocytes are increasingly becoming implicated in a variety of human diseases from leukodystrophies, congenital epilepsy syndromes, to neurodevelopmental

disorders, and beyond. Reactive astrocytes are a hallmark of nearly all major human CNS neurodegenerative conditions ( Zamanian et al., 2012). How do astrocytes do all this? Is there only one type of astrocyte? For many years, investigators have reported different morphologies of CNS astrocytes, but electrophysiological correlates have not been clearly demonstrated. Although astrocytes have traditionally been considered a homogeneous population of cells, steady reports of their increasingly diversified functional roles Ipatasertib nmr CCI-779 in vitro in mammals brings into question whether astrocyte subtypes may have been elaborated in complex brains to carry out enhanced regional functions. For example, expression profiling studies of astrocytes have generated databases suggesting heterogeneous

functions that may be organized according to brain region. Astrocyte cocultures from brain and spinal cord can show differential effects in regulation of neural stem cells, and indeed, SVZ stem cells, which bear similarities to astrocytes, have been shown to be heterogeneous in terms of their progeny output (Merkle et al., 2007). A new type of radial glia stem cell, the outer radial glia (oRG), appears to function in the mammalian brain to contribute further rounds of progeny production increasing brain size and complexity (Rowitch and Kriegstein, 2010). These findings are augmented by the notion that evolutionary pressure might be a driving force for diversified astrocyte functions, discussed further below. The diversity of functional roles continuously

carried out by glia make them indispensable GPX6 for CNS function. For example, glia have to balance neuronal requests for energy, maintain the concentration of multiple extracellular ions, secrete growth factors, survey the nervous system for injury, all while reading neuronal activity and taking part in some aspects of signaling. The complexity of glial functions raises multiple experimental obstacles. First, because glia do so much, they are indispensable in higher organisms and their manipulation often leads to neuronal demise and death of the organism. Second, it is challenging to measure any of these functions in vivo, never mind measuring them all at once.