Astrocyte heterogeneity: an underappreciated topic in neurobiology
Section snippets
Developmental heterogeneity
Different types of neurons originate from distinct progenitors. For example, cortical projection neurons originate from progenitors in the embryonic ventricular zone and they migrate radially to their final location. By contrast, cortical GABAergic interneurons arise from progenitors in the embryonic subpallium region and migrate tangentially to the cortex [9]. Astrocytes are found throughout the central nervous system. Do they arise from the same pool of progenitors or distinct groups of
Gene expression heterogeneity
Extensive evidence showed that astrocytes are highly heterogeneous with regard to their gene expression profiles. Using a novel translational profiling approach called translating ribosome affinity purification (TRAP), Heintz and colleagues compared translated mRNAs in cortical astrocytes, cerebellar astrocytes, and cerebellar Bergman glia, and reported substantial differences in gene expression between astrocytes from different brain regions [23••]. A recent microarray analysis of cultured
Physiological heterogeneity
Astrocytes have been traditionally described as a uniform group of cells with negative resting membrane potential, low input resistance, and extensive gap junction coupling. Recent studies indicate that astrocytes are highly diverse in their electrophysiological properties, calcium dynamics, and gap junction coupling.
The resting membrane potential of astrocytes varies widely, ranging from about −85 to −25 mV in acute hippocampal slices [47] and isolated optic nerves [48]. The distribution of
Functional heterogeneity
Astrocytes carry out a number of important functions including regulating extracellular concentrations of potassium ion and neurotransmitters, promoting synapse formation, regulating blood–brain-barrier, promoting neuronal survival and growth, producing neurons, and perhaps modulating synaptic transmission and plasticity. The effects of astrocytes on synaptic transmission are highly controversial. A number of studies employing a variety of pharmacological, optical, and genetic methods suggest
Heterogeneous response to injury and disease
Astrocytes respond to various injuries, infections, and diseases by reactive astrogliosis, which has both detrimental effects, for example, scar formation that prevents regrowth of injured axon and beneficial effects, for example, sealing the blood brain barrier. Astrocytes in epileptic brain both promote and oppose seizure development through a variety of mechanisms. Astrocytes play a key role in the pathogenesis of hepatic encephalopathy. Damage to astrocytes is seen in neurodegenerative
Conclusions
Astrocytes are a far more heterogeneous group of cells than was previously appreciated. Different subtypes of astrocytes differ in morphology, development, metabolism, physiology, and pathology. However, our current understanding of astrocyte heterogeneity, in particular the functional heterogeneity of astrocytes is still rudimentary. A large number of studies mentioned above are based on observations from cultured astrocytes in vitro. Improved culture methods that faithfully maintain in vivo
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
The authors apologize to colleagues whose work was not included because of the space restrictions.
References (92)
The mystery and magic of glia: a perspective on their roles in health and disease
Neuron
(2008)- et al.
Identification of positionally distinct astrocyte subtypes whose identities are specified by a homeodomain code
Cell
(2008) - et al.
Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis
Cell
(2009) - et al.
Brain astrocytes express region-specific surface glycoproteins in culture
Glia
(1988) - et al.
Region-specific regulation of preproenkephalin mRNA in cultured astrocytes
Brain Res Mol Brain Res
(1991) - et al.
Heterogeneous expression of carboxypeptidase E and proenkephalin mRNAs by cultured astrocytes
Brain Res
(1992) - et al.
Differential distribution of Kir4.1 in spinal cord astrocytes suggests regional differences in K+ homeostasis
J Neurophysiol
(2007) - et al.
Glial heterogeneity in expression of the inwardly rectifying K(+) channel, Kir4. 1, in adult rat CNS
Glia
(2000) - et al.
Metabotropic glutamate receptors in acutely isolated hippocampal astrocytes: developmental changes of mGluR5 mRNA and functional expression
Glia
(2000) - et al.
Cellular expression of P2Y and beta-AR receptor mRNAs and proteins in freshly isolated astrocytes and tissue sections from the CA1 region of P8-12 rat hippocampus
Brain Res Dev Brain Res
(2004)
Neurons modulate oxytocin receptor expression in rat cultured astrocytes: involvement of TGF-beta and membrane components
Glia
Differential erbB signaling in astrocytes from the cerebral cortex and the hypothalamus of the human brain
Glia
The GLT-1 and GLAST glutamate transporters are expressed on morphologically distinct astrocytes and regulated by neuronal activity in primary hippocampal cocultures
J Neurochem
Heterogeneity of astrocyte resting membrane potentials and intercellular coupling revealed by whole-cell and gramicidin-perforated patch recordings from cultured neocortical and hippocampal slice astrocytes
J Neurosci
Progeny of Olig2-expressing progenitors in the gray and white matter of the adult mouse cerebral cortex
J Neurosci
Astrocytic Connectivity in the Hippocampus
Neuron Glia Biol
Glutamate-mediated astrocyte-neuron signalling
Nature
Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors
Neuron
Selective stimulation of astrocyte calcium in situ does not affect neuronal excitatory synaptic activity
Neuron
Hippocampal short- and long-term plasticity are not modulated by astrocyte Ca2+ signaling
Science
Glial heterogeneity may define the three-dimensional shape of mouse mesencephalic dopaminergic neurones
Nature
GABAA receptor-expressing astrocytes in the supraoptic nucleus lack glutamate uptake and receptor currents
Glia
Neuroglia
Two types of astrocytes in cultures of developing rat white matter: differences in morphology, surface gangliosides, and growth characteristics
J Neurosci
Morphologic heterogeneity of human adult astrocytes in culture: correlation with HLA-DR expression
J Neurosci Res
Astrocyte subtypes in the rat olfactory bulb: morphological heterogeneity and differential laminar distribution
J Comp Neurol
Determinants of regional and local diversity within the astroglial lineage of the normal central nervous system
J Neurochem
Heterogeneity in astrocyte morphology and physiology
Brain Res Rev
Astrocyte heterogeneity or homogeneity
Cell migration in the forebrain
Annu Rev Neurosci
Specification of astrocytes by bHLH protein SCL in a restricted region of the neural tube
Nature
Organization and postembryonic development of glial cells in the adult central brain of Drosophila
J Neurosci
Ensheathing glia function as phagocytes in the adult Drosophila brain
J Neurosci
The glial nature of embryonic and adult neural stem cells
Annu Rev Neurosci
Two distinct subpopulations of nestin-positive cells in adult mouse dentate gyrus
J Neurosci
Reinduction of ErbB2 in astrocytes promotes radial glial progenitor identity in adult cerebral cortex
Genes Dev
Microarray analyses reveal regional astrocyte heterogeneity with implications for neurofibromatosis type 1 (NF1)-regulated glial proliferation
Glia
Trophic interactions between astroglial cells and hippocampal neurons in culture
Science
Slit is the midline repellent for the robo receptor in Drosophila
Cell
Control of synapse number by glia
Science
Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis
Cell
Application of a translational profiling approach for the comparative analysis of CNS cell types
Cell
Spinal cord astrocytes in vitro: phenotypic diversity and sodium channel immunoreactivity
Glia
Differential assembly of inwardly rectifying K+ channel subunits, Kir4. 1 and Kir5. 1, in brain astrocytes
J Biol Chem
Heterogeneity of Kir4.1 channel expression in glia revealed by mouse transgenesis
Glia
Novel regional and developmental NMDA receptor expression patterns uncovered in NR2C subunit-beta-galactosidase knock-in mice
Mol Cell Neurosci
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