1,721,094 research outputs found
ATP mediates calcium signaling between astrocytes and microglial cells : modulation by IFN-gamma
No full textCalcium-mediated intercellular communication is a mechanism by which astrocytes communicate with each other and modulate the activity of adjacent cells, including neurons and oligodendrocytes. We have investigated whether microglia, the immune effector cells involved in several diseases of the CNS, are actively involved in this communication network. To address this issue, we analyzed calcium dynamics in fura-2-loaded cocultures of astrocytes and microglia under physiological conditions and in the presence of the inflammatory cytokine IFN-gamma. The intracellular calcium increases in astrocytes, occurring spontaneously or as a result of mechanical or bradykinin stimulation, induced the release of ATP, which, in turn, was responsible for triggering a delayed calcium response in microglial cells. Repeated stimulations of microglial cells by astrocyte-released ATP activated P2X(7) purinergic receptor on microglial cells and greatly increased membrane permeability, eventually leading to microglial apoptosis. IFN-gamma increased ATP release and potentiated the P2X(7)-mediated cytolytic effect. This is the first study showing that ATP mediates a form of calcium signaling between astrocytes and microglia. This mechanism of intercellular communication may be involved in controlling the number and function of microglial cells under pathophysiologic CNS conditions
ATP in neuron-glia bidirectional signalling
No full textATP accomplishes important roles in brain, where it functions as neurotransmitter or co-transmitter, being stored and released either as single mediator or together with other neuromodulators. In the last years, the purinergic system has emerged as the most relevant mechanism for intercellular signalling in the nervous system, affecting communication between many types of neurons and all types of glia. In this review, we will focus on recently reported data which describe the role of ATP in bidirectional signalling between neurons and different populations of glial cells, in both peripheral and central system. (C) 2010 Elsevier B.V. All rights reserved
Pathophysiological roles of P2 receptors in glial cells
No full textExtracellular nucleotides act through specific receptors on target cells: the seven ionotropic P2X and the eight G protein-coupled P2Y receptors. All these receptors are expressed by brain astroglia and microglia. In astrocytes, P2 receptors have been implicated in short-term calcium-dependent cell–cell communication. Upon mechanical stimulation or activation by other transmitters, astrocytes release ATP and respond to ATP with a propagating wave of intracellular calcium increases, allowing a homotypic astrocyte–astrocyte communication, as well as an heterotypic signalling which also involves neurons, oligodendrocytes and microglia. Astrocytic P2 receptors also mediate reactive astrogliosis, a reaction contributing to neuronal death in neurodegenerative diseases. Signalling leading to inflammatory astrogliosis involves induction of cyclo-oxygenase 2 through stimulation of ERK1,2 and of the transcriptional factors AP-1 and NF-κB. Microglia also express several P2 receptors linked to intracellular calcium increases. P2 receptor subtypes are differentially regulated by typical proinflammatory signals for these cells (e.g. lipopolysaccharide), suggesting specific roles in brain immune responses. Globally, these findings highlight the roles of P2 receptors in glial cell pathophysiology suggesting a contribution to neurodegenerative diseases characterized by excessive gliosis and neuro-inflammation. They also open up the possibility of modulating brain damage by ligands selectively targeting the specific P2 receptor subtypes involved in the gliotic response
Increase of myeloid microvesicles in the cerebrospinal fluid as biomarkers of microglia/microphage activation in neurological disorders
No full textThe present invention relates to a method for the diagnosis and/or prognosis of a
neurological disease characterized by an inflammatory process as well as a method for
predicting and /or monitoring the efficacy of a treatment for a neurological pathology. The
methods are based on the measurement of the amount of myeloid derived microvesicles in
a cerebrospinal fluid sample
Spatial changes in calcium signaling during the establishment of neuronal polarity and synaptogenesis
Full text linkCalcium imaging techniques were used to obtain a clear although indirect evidence about the distribution of functional glutamate receptors of NMDA and non-NMDA type in cultured hippocampal neurons during establishment of polarity and synaptogenesis. Glutamate receptors were expressed and were already functional as early as one day after plating. At this stage NMDA and non-NMDA receptors were distributed in all plasmalemmal areas. During the establishment of neuronal polarity, responses to either types of glutamate receptors became restricted to the soma and dendrites. Compartmentalization of glutamate receptors occurred at stages of development when synaptic vesicles were already fully segregated to the axon. Formation of synapses was accompanied by a further redistribution of receptors, which segregated to synapse-enriched portions of dendrites. Receptor compartmentalization and dendritic redistribution as well as accumulation of synaptic vesicles at synaptic sites occurred also in neurons cultured in the presence of either the sodium channel blocker tetrodotoxin or glutamate receptor antagonists. These results indicate that signals generated by neuronal electrical activity or receptor activation are not involved in the establishment of neuronal polarity and synaptogenesis
Purinergic neuron/glia communication in the spinal-trigeminal system in vitro and in vivo: implications for basic mechanisms of pain transmission
No full textIt is now known that glial cells directly participate to the genesis and maintenance of chronic pain, both in the central and in the peripheral nervous system, through their functional cross-talk with pain-transducing neurons [1]. The whole molecular network at the basis of this neuron-to-glia communication is still largely unknown, and the purinergic system is likely to play a key role in close conjunction with other pain-transducing systems [2, 3]. Therefore, we decided to study the contribution of the G protein-coupled P2Y purinergic receptors in pain transmission in the spinal-trigeminal system both in vitro and in vivo. In primary mixed trigeminal cultures, we showed that the pro-algogenic molecule bradykinin potentiates P2Y receptors expressed by satellite glial cells (SGCs) [4] through the neuronal release of calcitonin gene related peptide (CGRP), which in turn activates the ERK1/2 pathways in SGCs [5]. Interestingly, in cultures from a genetic mouse model of familial hemiplegic migraine we observed an increased CGRP release and an up-regulation in the number of SGCs showing functional P2Y receptors, suggesting that the role of the purinergic system in neuron-glia crosstalk is even more important under pathological conditions [5].
To study the pro- or anti-algogenic role of specific P2Y receptor subtypes in vivo, we next set up a sub-chronic inflammatory model in vivo by injecting complete Freund adjuvant (CFA) into the temporomandibular joint (TMJ). CFA-injected animals showed mechanical allodynia and TMJ edema, accompanied by a strong increase in the number of reactive SGCs and resident macrophages in the TG, and by microglial activation in the ipsilateral medulla oblongata [6]. We are now evaluating the pro- or anti-algogenic role of specific P2Y-receptor subtypes in pain transduction.
Overall, our results suggest that P2Y receptors on glial cells might represent innovative targets for the development of effective analgesic drugs.
References
[1] M. Takeda, M. Takahashi, S. Matsumoto. Contribution of the activation of satellite glia in sensory ganglia to pathological pain. Neuroscience Biobehavioural Reviews, 33, 784-792, 2009.
[2] D. Donnelly-Roberts, S. McGaraughty, C.C. Shieh, P. Honore, M.F. Jarvis. Painful purinergic receptors. Journal of Pharmacology and Experimental Therapeutics, 324, 409-415, 2009.
[3] G. Villa, M. Fumagalli, C. Verderio, M.P. Abbracchio, S. Ceruti. Expression and contribution of satellite glial cells purinoceptors to pain transmission in sensory ganglia: an update. Neuron Glia Biol, 6, 31-42, 2010.
[4] S. Ceruti, M. Fumagalli, G. Villa, C. Verderio, M.P. Abbracchio. Purinoceptor-mediated calcium signaling in primary neuron-glia trigeminal cultures. Cell Calcium, 43, 576-90, 2008.
[5] S. Ceruti, G. Villa, M. Fumagalli, L. Colombo, G. Magni, M. Zanardelli, E. Fabbretti, C. Verderio, A.M. van den Maagdenberg, A. Nistri, M.P. Abbracchio. Calcitonin Gene-Related Peptide-Mediated Enhancement of Purinergic Neuron/Glia Communication by the Algogenic Factor Bradykinin in Mouse Trigeminal Ganglia from Wild-Type and R192Q Cav2.1 Knock-In Mice: Implications for Basic Mechanisms of Migraine Pain. J Neurosci, 31, 3638-3649, 2011.
[6] G. Villa, S. Ceruti, M. Zanardelli, G. Magni, L. Jasmin, P.T. Ohara, M.P. Abbracchio. Temporomandibular join inflammation activates glial and immune cells in both the trigeminal ganglia and the spinal trigeminal nucleus. Mol Pain, 6, 89, 2010
Vesicle recycling in developing neurons : how to build a presynaptic terminal
No full textOver the past decade, evidence has accumulated indicating that, during development, the construction of synapses--the sites of communication between neurons--might rely on the utilization of preassembled sets of synaptic proteins, which have already accumulated in the axon and are highly mobile, before getting recruited to the sites of contact with the postsynaptic neuron. In this review, we discuss evidence from most recent publications pointing to the existence of active vesicle traffic and turnover in developing neurons, which lead to the construction of new synaptic sites
Purinergic P2Y(2) receptors on satellite glial cells as new potential targets for the pharmacological control of trigeminal sensitization
No full textSynaptogenesis in hippocampal cultures
No full textHippocampal cultures offer unique advantages for the study of neuronal development and synaptogenesis. Studies performed on this model enabled dissection of the temporal sequence of events which lead to the differentiation of pre- and postsynaptic compartments
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