Different Mechanisms Promote Astrocyte Ca<sup>2+</sup>Waves and Spreading Depression in the Mouse Neocortex

Peters, Oliver; Schipke, Carola G.; Hashimoto, Yoshinori; Kettenmann, Helmut

doi:10.1523/jneurosci.23-30-09888.2003

Cited by 186 publications

(141 citation statements)

References 42 publications

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“…In line with previous in vitro (10,22,32) and in vivo (14) studies, we found that activation of the NMDA glutamate receptor is required for CSD, as demonstrated by the inhibition of CSD by the NMDA receptor antagonist L-APV. Conversely, CSD is not affected by blockade of the AMPA glutamate receptor.…”

Section: Discussionsupporting

confidence: 92%

Critical role of calcitonin gene-related peptide receptors in cortical spreading depression

Tozzi

Iure

Filippo

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

126

117

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Cortical spreading depression (CSD) is a key pathogenetic step in migraine with aura. Dysfunctions of voltage-dependent and receptor-operated channels have been implicated in the generation of CSD and in the pathophysiology of migraine. Although a known correlation exists between migraine and release of the calcitonin gene-related peptide (CGRP), the possibility that CGRP is involved in CSD has not been examined in detail. We analyzed the pharmacological mechanisms underlying CSD and investigated the possibility that endogenous CGRP contributes to this phenomenon. CSD was analyzed in rat neocortical slices by imaging of the intrinsic optical signal. CSD was measured as the percentage of the maximal surface of a cortical slice covered by the propagation of intrinsic optical signal changes during an induction episode. Reproducible CSD episodes were induced through repetitive elevations of extracellular potassium concentration. AMPA glutamate receptor antagonism did not inhibit CSD, whereas NMDA receptor antagonism did inhibit CSD. Blockade of voltage-dependent sodium channels by TTX also reduced CSD. CSD was also decreased by the antiepileptic drug topiramate, but not by carbamazepine. Interestingly, endogenous CGRP was released in the cortical tissue in a calcium-dependent manner during CSD, and three different CGRP receptor antagonists had a dose-dependent inhibitory effect on CSD, suggesting a critical role of CGRP in this phenomenon. Our findings show that both glutamate NMDA receptors and voltage-dependent sodium channels play roles in CSD. They also demonstrate that CGRP antagonism reduces CSD, supporting the possible use of drugs targeting central CGRP receptors as antimigraine agents.M igraine is a common episodic headache disorder characterized by attacks that include various combinations of headache and neurologic, gastrointestinal, and autonomic symptoms. It is among the most common neurologic conditions, affecting ∼12-20% of the population. The International Headache Society classifies migraine into migraine without aura and migraine with aura, with aura defined as the complex of focal neurologic symptoms that most often precedes or accompanies an attack (1-3).Cortical spreading depression (CSD) is thought to represent a key pathogenetic step in migraine with aura (4, 5). First reported by Leão in 1944 (6), CSD is a wave of electrical activity (excitation followed by depression) that moves across the cerebral cortex after electrical or chemical stimulation. The pivotal event in the generation and propagation of CSD is a marked decrease in neuronal membrane resistance associated with massive increases in extracellular K + and neurotransmitters, as well as increases in intracellular Na + and Ca 2+ (7-9). Genetic and environmental factors modulate individual susceptibility by lowering the CSD threshold, and cortical excitation can cause sufficient elevation in extracellular K + and glutamate to initiate CSD (5,7,8,(10)(11)(12)(13)(14). Conversely, the CSD threshold also may be increased by factors that re...

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Section: Discussionsupporting

confidence: 92%

Critical role of calcitonin gene-related peptide receptors in cortical spreading depression

Tozzi

Iure

Filippo

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

126

117

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“…By an appropriate protocol, we preferentially loaded the Ca 2ϩ sensor Fluo-4-acetoxymethylester into astrocytes (31). Superfusion with NAADP ϩ (5 M, duration of application 2-3 min) triggered an increase in Fluo-4 fluorescence, reflecting the change in [Ca 2ϩ ] i in astrocytes (Fig.…”

Section: Naadp ϩ Induced Different Types Of Ca 2ϩmentioning

confidence: 99%

Extracellular Application of Nicotinic Acid Adenine Dinucleotide Phosphate Induces Ca2+ Signaling in Astrocytes in Situ

Heidemann

Schipke

Kettenmann

2005

Journal of Biological Chemistry

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Astrocytes are in intimate contact with neurons, in particular with synapses, and are able to sense, react to, and even influence neuronal activity. The astrocytic response to neuronal activity can be most readily detected by observing changes in the intracellular Ca 2ϩ concentration mediated via transmitter receptors (e.g. glutamate, GABA (␥-aminobutyric acid), or acetylcholine) or via other messengers, such as nitric oxide. Ca 2ϩ increases can occur by Ca 2ϩ influx via the plasma membrane as found for the nitric oxide-mediated neuron-glia signaling in the cerebellum (1). Ca 2ϩ can furthermore be released from intracellular stores by activation of metabotropic receptors such as GABA B receptors, which mediate neuron-glia signaling in the hippocampus (2). Indeed, astrocytes express a variety of receptors linked to the Ca 2ϩ mobilization from intracellular stores (3). To produce specific signals with one and the same messenger (Ca 2ϩ ), several second messenger pathways and different sources of Ca 2ϩ are involved. It seems important, at the current stage, to decipher the astrocytic Ca 2ϩ code, since this would lead to further understanding of how these cells can react to and influence the neuronal network.The best investigated second messenger linking activation of metabotropic receptors and Ca 2ϩ release is inositol 1,4,5-trisphosphate (IP 3 ). 2The importance of other intracellular messengers, such as cyclic ADPribose (cADPR), is less well understood (4) or still hypothetical as for the two sphingomyelin metabolites sphingosine 1-phosphate (5) and sphingosylphosphorylcholine (6). Almost a decade ago, a novel intracellular Ca 2ϩ -releasing second messenger was identified in sea urchin eggs, nicotinic acid adenine dinucleotide phosphate (NAADP ؉ ) (7), which binds to an unknown receptor. Since its discovery, there is increasing evidence that NAADP ϩ also has a physiological role in Ca 2ϩ signal transduction in vertebrates, including mammalian cells (8). In the vertebrate nervous system, intracellular Ca 2ϩ release by NAADP ϩ has only been demonstrated from rat brain microsome preparations (9) and in frog motoneurons (10). NAADP ϩ -specific binding sites are found in gray and white matter of rat brain, but the cellular specificity of the binding site has not yet been determined (11). The major way of NAADP ϩ synthesis in mammalian tissue takes place under acidic conditions and in the presence of nicotinic acid from NADP ϩ by the type II transmembrane glycoprotein ADP-ribosyl cyclase CD38. In a neutral or alkaline environment, CD38 exclusively catalyzes the conversion of NAD ϩ into cADPR (12). Apart from cell membrane localization, CD38 has been located to various intracellular organelle membranes and can moreover be internalized by endocytosis (13). Therefore, NAADP ϩ synthesis most likely takes place in membranes of intracellular acidic organelles such as lysosomes or late endosomes, whereas CD38 in the plasma membrane synthesizes cADPR. Regarding the mammalian central nervous system, CD38 expression was demonstr...

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“…Glial Ca 2+ waves that propagate both within and between cells do occur in brain tissue (Peters et al, 2003) and the retina . In retinal astrocytes and Müller cells, stimulation of one cell region results in a Ca 2+ increase that propagates into other cells regions (Newman, 2001b).…”

Section: Glia To Glia Signalingmentioning

confidence: 99%

A dialogue between glia and neurons in the retina: modulation of neuronal excitability

Newman

2004

Neuron Glia Biol.

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Bidirectional signaling between neurons and glial cells has been demonstrated in brain slices and is believed to mediate glial modulation of synaptic transmission in the CNS. Our laboratory has characterized similar neuron-glia signaling in the mammalian retina. We find that light-evoked neuronal activity elicits Ca 2+ increases in Müller cells, which are specialized retinal glial cells. Neuron to glia signaling is likely mediated by the release of ATP from neurons and is potentiated by adenosine. Glia to neuron signaling has also been observed and is mediated by several mechanisms. Stimulation of glial cells can result in either facilitation or depression of synaptic transmission. Release of D-serine from Müller cells might also potentiate NMDA receptor transmission. Müller cells directly inhibit ganglion cells by releasing ATP, which, following hydrolysis to adenosine, activates neuronal A 1 receptors. The existence of bidirectional signaling mechanisms indicates that glial cells participate in information processing in the retina.

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Different Mechanisms Promote Astrocyte Ca²⁺Waves and Spreading Depression in the Mouse Neocortex

Cited by 186 publications

References 42 publications

Critical role of calcitonin gene-related peptide receptors in cortical spreading depression

Critical role of calcitonin gene-related peptide receptors in cortical spreading depression

Extracellular Application of Nicotinic Acid Adenine Dinucleotide Phosphate Induces Ca2+ Signaling in Astrocytes in Situ

A dialogue between glia and neurons in the retina: modulation of neuronal excitability

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Different Mechanisms Promote Astrocyte Ca2+Waves and Spreading Depression in the Mouse Neocortex

Cited by 186 publications

References 42 publications

Critical role of calcitonin gene-related peptide receptors in cortical spreading depression

Critical role of calcitonin gene-related peptide receptors in cortical spreading depression

Extracellular Application of Nicotinic Acid Adenine Dinucleotide Phosphate Induces Ca2+ Signaling in Astrocytes in Situ

A dialogue between glia and neurons in the retina: modulation of neuronal excitability

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Different Mechanisms Promote Astrocyte Ca²⁺Waves and Spreading Depression in the Mouse Neocortex