Neuronal regulation of astrocyte morphology in vitro is mediated by GABAergic signaling

The addition of isolated neurons to monolayers of cultured astrocytes induced a morphological change in the astrocytes that came into contact with the added neuronal cell bodies or neurites. The change, which included an increase in the complexity of cell shape, took at least 3 days to become detectable and was enhanced in proportion to the number of attached neurons. Astrocytes that did not make contact with any neurons had a less complex contour, comparable to those in control cultures with no neurons added. Treatment of neuron‐astrocyte cocultures with a sodium channel blocker, tetrodotoxin, suppressed the neuron‐induced morphological changes in astrocytes. A GABAA‐receptor antagonist, bicuculline, mimicked the inhibitory effect of tetrodotoxin. In cultures without added neurons, morphological alteration of astrocytes was also observed when cultures were incubated for 1 or more days with exogenous GABA together with a GABA‐uptake inhibitor, 4,5,6,7‐tetrahydroisoxazolo[4,5‐c]pyridin‐3‐ol. The effect of exogenous GABA was mimicked by treatment with a GABAA‐receptor agonist, muscimol, and blocked by bicuculline treatment. These results suggest that GABA released from neurons with their activity serves as a signal from neurons to astrocytes that triggers the morphological change in astrocytes through the activation of GABAA receptors. GLIA 20:1‐9, 1997. © 1997 Wiley‐Liss, Inc.

[1]  M. Nedergaard,et al.  Direct signaling from astrocytes to neurons in cultures of mammalian brain cells. , 1994, Science.

[2]  Theresa A. Jones,et al.  Ultrastructural Evidence for Increased Contact between Astrocytes and Synapses in Rats Reared in a Complex Environment , 1996, Neurobiology of Learning and Memory.

[3]  K. H. Backus,et al.  γ-Aminobutyric acid opens Cl-channels in cultured astrocytes , 1987, Brain Research.

[4]  M. Leon.  Plasticity of olfactory output circuits related to early olfactory learning , 1987, Trends in Neurosciences.

[5]  J. Bormann,et al.  Patch-clamp study of gamma-aminobutyric acid receptor Cl- channels in cultured astrocytes. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[6]  J. Turner,et al.  Morphology of astroglial cells is controlled by beta-adrenergic receptors , 1987, The Journal of cell biology.

[7]  A. Baba,et al.  Endothelins modulate dibutyryl cAMP-induced stellation of cultured astrocytes , 1993, Brain Research.

[8]  E. Hansson,et al.  Receptor regulation of the glutamate, GABA and taurine high-affinity uptake into astrocytes in primary culture , 1991, Brain Research.

[9]  W. Greenough,et al.  Glial hypertrophy is associated with synaptogenesis following motor‐skill learning, but not with angiogenesis following exercise , 1994, Glia.

[10]  S. Murphy,et al.  Effects of Neurotransmitters on Astrocyte Glycogen Stores In Vitro , 1988, Journal of neurochemistry.

[11]  K. Subbarao,et al.  Desensitization of gamma-aminobutyric acid receptor from rat brain: two distinguishable receptors on the same membrane. , 1987, Biochemistry.

[12]  J. P. Schwartz.  Neurotransmitters as neurotrophic factors: a new set of functions. , 1992, International review of neurobiology.

[13]  M. Leon,et al.  Neuroethology of olfactory preference development. , 1992, Journal of neurobiology.

[14]  M. Hatten,et al.  Neuronal regulation of astroglial morphology and proliferation in vitro , 1985, The Journal of cell biology.

[15]  E. Azmitia,et al.  Stimulation of astroglial 5-HT1A receptors releases the serotonergic growth factor, protein S-100, and alters astroglial morphology , 1990, Brain Research.

[16]  D. Keyser,et al.  Synaptic transmission in the hippocampus: Critical role for glial cells , 1994, Glia.

[17]  S. Meiners,et al.  A distinct subset of tenascin/CS-6-PG-rich astrocytes restricts neuronal growth in vitro , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[18]  H. M. Geller,et al.  Astrocyte topography and tenascin cytotactin expression: correlation with the ability to support neuritic outgrowth. , 1990, Brain research. Developmental brain research.

[19]  V. Gallo,et al.  Excitatory amino acid receptors in glia: Different subtypes for distinct functions? , 1995, Journal of neuroscience research.

[20]  Arne Schousboe,et al.  Transport and Metabolism of Glutamate and Gaba in Neurons and Glial Cells , 1981 .

[21]  M. Corner,et al.  Development of Neurons and Glial Cells in Cerebral Cortex, Cultured in the Presence or Absence of Bioelectric Activity: Morphological Observations , 1991, The European journal of neuroscience.

[22]  H. Kettenmann,et al.  Pharmacological properties of gamma-aminobutyric acid-, glutamate-, and aspartate-induced depolarizations in cultured astrocytes , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  S. Furukawa,et al.  Catecholamines increase nerve growth factor mRNA content in both mouse astroglial cells and fibroblast cells , 1989, FEBS letters.

[24]  A. Schousboe,et al.  Anticonvulsant activity of the glial-selective GABA uptake inhibitor, THPO , 1983, Neuropharmacology.

[25]  J. Olavarria,et al.  Reduced retinal activity increases GFAP immunoreactivity in rat lateral geniculate nucleus , 1994, Brain Research.

[26]  Stephen J. Smith,et al.  The excitatory neurotransmitter glutamate causes filopodia formation in cultured hippocampal astrocytes , 1990, Glia.

[27]  R. Lindsay,et al.  Changes in neurotrophic factor expression and receptor activation following exposure of hippocampal neuron/astrocyte cocultures to kainic acid , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[28]  James E. Vaughn,et al.  Glutamate decarboxylase localization in neurons of the olfactory bulb , 1977, Brain Research.

[29]  H. Kimelberg,et al.  EFFECTS OF NOREPINEPHRINE ON THE MORPHOLOGY AND SOME ENZYME ACTIVITIES OF PRIMARY MONOLAYER CULTURES FROM RAT BRAIN , 1978, Journal of neurochemistry.

[30]  M. Hatten.  Neuronal inhibition of astroglial cell proliferation is membrane mediated , 1987, The Journal of cell biology.

[31]  P. Eriksson,et al.  GABA induces Ca2+ transients in astrocytes , 1993, Neuroscience.

[32]  C. Mason,et al.  Astroglial differentiation is required for support of neurite outgrowth , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[33]  E. Hansson,et al.  Regulation of glutamate and GABA transport by adrenoceptors in primary astroglial cell cultures. , 1989, Life sciences.

[34]  H. Kettenmann,et al.  GABAA/benzodiazepine receptors in acutely isolated hippocampal astrocytes , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[35]  K. McCarthy,et al.  Analysis of Cyclic AMP‐Dependent Changes in Intermediate Filament Protein Phosphorylation and Cell Morphology in Cultured Astroglia , 1986, Journal of neurochemistry.

[36]  R. Liem,et al.  C17, a retrovirally immortalized neuronal cell line, inhibits the proliferation of astrocytes and astrocytoma cells by a contact‐mediated mechanism , 1990, Glia.

[37]  H. Kettenmann,et al.  GABA-activated Cl- channels in astrocytes of hippocampal slices , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[38]  Yutaka Koyama,et al.  A morphological study on glutamate-induced swelling of cultured astrocytes: Involvement of calcium and chloride ion mechanisms , 1991, Neuroscience Letters.

[39]  S. Mennerick,et al.  Components of glial responses to exogenous and synaptic glutamate in rat hippocampal microcultures , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[40]  M. Leon,et al.  Elaboration of glial cell processes in the rat olfactory bulb associated with early learning , 1993, Brain Research.

[41]  D. Corey,et al.  Ion channels in vertebrate glia. , 1990, Annual review of neuroscience.

[42]  V. M. Neto,et al.  Thyroid hormone and conditioned medium effects on astroglial cells from hypothyroid and normal rat brain: Factor secretion, cell differentiation, and proliferation , 1995, Journal of neuroscience research.

[43]  T. Grisar,et al.  Astroglial Cells Express Large Amounts of GABAA Receptor Proteins in Mature Brain , 1995, Journal of neurochemistry.

[44]  D. Wilson,et al.  Odor familiarity alters mitral cell response in the olfactory bulb of neonatal rats. , 1985, Brain research.

[45]  K. McCarthy,et al.  Astroglial Gap Junction Communication Is Increased by Treatment with Either Glutamate or High K+ Concentration , 1994, Journal of neurochemistry.

[46]  T. Kosaka,et al.  An aspect of the organization of the GABAergic system in the rat main olfactory bulb: laminar distribution of immunohistochemically defined subpopulations of GABAergic neurons , 1987, Brain Research.

[47]  J. Goldman,et al.  Cyclic AMP-induced shape changes of astrocytes are accompanied by rapid depolymerization of actin , 1990, Brain Research.

[48]  P. Magistretti,et al.  Vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, and noradrenaline induce the transcription factors CCAAT/enhancer binding protein (C/EBP)-beta and C/EBP delta in mouse cortical astrocytes: involvement in cAMP-regulated glycogen metabolism , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[49]  Steven Mennerick,et al.  Glial contributions to excitatory neurotransmission in cultured hippocampal cells , 1994, Nature.

[50]  W. Greenough,et al.  Plasticity of GFAP-immunoreactive astrocyte size and number in visual cortex of rats reared in complex environments , 1991, Brain Research.

[51]  C. Müller.  A role for glial cells in activity-dependent central nervous plasticity? Review and hypothesis. , 1992, International review of neurobiology.

[52]  C. Gall,et al.  Odor-induced increases in c-fos mRNA expression reveal an anatomical "unit" for odor processing in olfactory bulb. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[53]  G. Orban,et al.  Immunocytochemical detection of astrocyte GABAA receptors in cat visual cortex. , 1993, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.