XI European Meeting on Glial Cell Function in Health and Disease

Overview Session Overview Sessionprint print  

July 3, 2013 - Room 2 9:00am - 10:50am
Workshop III: Astrocyte Heterogeneity and Transcriptome Analysis

Organized by
Maiken Nedergard (University of Rochester, USA)
Alexei Verkhratsky (University of Manchester, UK)



*Alexei Verkhratsky 1
1 The University of Manchester, , Manchester, United Kingdom
Abstract text :



Evolution, physiology and pathophysiology of neuroglia

*Alexei Verkhratsky 1
1 The University of Manchester, , Manchester, United Kingdom
Abstract text :

The nervous system in mammals represents complex network formed by several distinct cell types of neural and non-neural origin. In the course of evolution from most primitive diffuse nervous system to the human brain these cellular types underwent remarkable degree of specialisation. Neurones become perfect elements for signalling and information processing, whereas housekeeping functions went to the neuroglia, which have themselves specialised into many types of cells to provide for specific aspects of nervous system homeostasis. Homeostatic function of neuroglia is executed at many levels, and includes whole body and organ homeostasis (for example astrocytes control the emergence and maintenance of the CNS, peripheral glia are essential for communication between the CNS and the body, and  enteric glia are essential for every aspect of gastrointestinal function), cellular homeostasis (e.g. astroglia and NG2-glia are both stem elements), morphological homeostasis (glia define the migratory pathways for neural cells during development, shape the nervous system cyto-architecture, and control synaptogenesis/synaptic pruning, whereas myelinating glia maintain the structural integrity of nerves), molecular homeostasis (which is represented by neuroglial regulation of ion, neurotransmitter and neurohormone concentration in the extracellular spaces around neurons), metabolic homeostasis (e.g. neuroglial cells store energy substrates in a form of glycogen and supply neurones with lactate), long-range signalling homeostasis (by myelination provided by oligodendroglia and Schwann cells), and defensive homeostasis (represented by astrogliosis and activation of microglia in the CNS, Wallerian degeneration in CNS and PNS, and immune reactions of enteric glia, all these reactions providing fundamental defence for neural tissue). Moreover, some neuroglial cells act as chemosensitive elements of the brain that perceive systemic fluctuations in CO2, pH and Na and thus regulate behavioural and systemic homeostatic physiological responses. Since any brain disease results from failure in brain homeostasis, neuroglia are involved in many, if not all, aspects of neurological disorders and hence neuroglia may represent a novel target for medical intervention in treatment of neurological diseases.


Structural heterogeneity of astrocytic cells in vertebrate CNS

*Andreas Reichenbach 1
1 Universität Leipzig, Paul Flechsig Institute of Brain Research, Leipzig, Germany
Abstract text :

The morphology of astroglia is very diverse. The soma of the cells give rise to one or several ‘primary’ or ‘stem’ processes which may bear many secondary branches. Much of this diversity is related to structural and functional interactions of a given cell with its microenvironment, which includes on the one side the neurons and on the other side, blood vessels, the pia mater, and/or the ventricular space. Typical astrocytes are more or less star-shaped but their structure (and function) depends on the specific specialization of the surrounding tissue such as cortex, brain stem nuclei, spinal cord, etc. The differentiated descendants of the fetal radial glia are termed tanycytes (in brain) or Müller cells (in retina). Despite of displaying a very complex structure, it is now clear that astroglial cell processes are by no means unchangeable, static structures. After the general shape of an astroglial cell has been established in ontogenesis, its processes develop in (mutual) dependence on the developing neuronal cell processes and synapses. If different species are compared, it must be kept in mind that the total size of a mammal correlates with the size of its brain as well as with the size of its neurons. In parallel, the absolute and relative number of glial cells and their size increases. This appears to be genetically controlled, at least partially. One example is constituted by polyploid amphibians and lungfish; the increasing DNA content causes an enlargement of both the cell nuclei and of the cells themselves. Recently it was shown by Maiken Nedergaard and colleagues who transplanted human astrocytes into mouse brains; they found that the human astrocytes were much larger than the neighboring murine host astrocytes. Generally it is difficult to say how much of the different size of astrocytes in different animals is due to genetic instruction or to adaptation to the environment. For instance, cerebellar Bergmann glial cells have to span the entire thickness of the molecular layer; depending on the number and thickness of neuronal cell processes, this layer is much thinner in small animals than in big ones. Accordingly, the Bergmann glial cell processes are much elongated in large species. In summary, there exist a large number of genetic and epigenetic factors enforcing astrocytic heterogeneity.


How glial are neural stem cells – insights from genome-wide analysis

*Magdalena Götz 1
1 Helmholtz Center Munich, Institute of Stem Cell Research, Munich, Germany
Abstract text :

Since the discovery of radial glial cells in the developing brain, an issue of debate is to which extent these are ‘bona-fide’ glial cells, or rather neuroepithelial cells that happen to express a few genes in common with astroglial cells. This debate was kept alive by hinging on few so-called ‘markers’, such as GFAP, glutamine synthase, GLAST, Glt-1 or S100b. However, cell type definition should not hinge on a few proteins, but rather – besides other criteria, such as ultrastructure or function – by genomewide expression analysis and unsupervised clustering encompassing all genes expressed and their respective levels.

We have done this by using Fluorescent-activated cell sorting to isolate RNA from ependymal cells, astrocytes, oligodendrocyte progenitors and adult neural stem cells in the adult mouse forebrain (Beckervordersandforth et al., 2010; Götz, Dimou, Sirko, unpublished) and compared their gene expression to their counterparts in the developing forebrain, the radial glial cells (Pinto et al., 2008). This revealed not only that the ‘markers’ we rely on are actually expressed commonly by astrocytes, ependymal cells and adult neural stem cells – just at different levels (Beckervordersandforth et al., 2010), but also striking similarities between adult neural stem cells and astrocytes and ependymal cells, while the radial glial cells from the embryonic brain clustered closely with neuroblasts of the adult subependymal zone. Thus, embryonic and adult neural stem cells are rather different, a concept which is further substantiated by the transcriptional regulators of their fate. This and further conceptual insights into differences and similarities of distinct glial subtypes and neural stem and progenitor cells will be discussed.