P2 receptor-stimulation influences axonal outgrowth in the developing hippocampus in vitro

Heine, Claudia; Heimrich, Bernd; Vogt, Johannes; Wegner, Anne; Illéš, Peter; Franke, Heike

doi:10.1016/j.neuroscience.2005.11.056

Cited by 40 publications

(27 citation statements)

References 65 publications

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“…In mouse olfactory epithelium, ATPγS induced proliferation and neuronal differentiation [43] whereas in our study it abrogated E13.5-derived progenitor cells, in contrast to 2MeSATP. 2MeSATP was found to stimulate catecholamine release from chromaffin cells [44] or to promote neurite outgrowth in entorhino-hippocampal slice cocultures [45]. Thus, even though ADPβS, ATPγS and 2ClATP share their deleterious effect on progenitors they may exert their function via different mechanisms.…”

Section: P2xmentioning

confidence: 99%

Nucleotides affect neurogenesis and dopaminergic differentiation of mouse fetal midbrain-derived neural precursor cells

Delic

Zimmermann

2010

Purinergic Signalling

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The fetal midbrain is a preferred source for isolating and producing dopaminergic neurons for subsequent grafting and replacement of damaged or lost dopaminergic midbrain neurons. We analysed the potential of a variety of nucleotides and of adenosine to support dopaminergic neuron formation from primary mouse fetal midbrain-derived cells, harvested at E10.5 and at E13.5 and subjected to adherent cell culture. In contrast to cells derived at E13.5, cells derived at E10.5 have the potential to produce dopaminergic neurons in culture. These neurons express tyrosine hydroxylase and the dopamine transporter. The fetal ventral midbrain contained mRNA encoding almost all P2X and P2Y receptors, all adenosine receptors as well as the ectonucleotidases nucleoside triphosphate diphosphohydrolase 2 and tissue nonspecific alkaline phosphatase. Essentially, all components of the purinergic signalling pathway were also expressed by the cultured cells. ATP, ADPβS, 2MeSATP, 2ClATP and adenosine increased neuron formation. There was, however, no preference for the formation of dopaminergic neuronswith the exception of 2ClATP that increased the relative contribution of tyrosine hydroxylase-positive neurons. In cells isolated at E13.5 UTP promoted neuron survival but ADPβS and ATPγS essentially eliminated neurons. These data showed that the outcome of nucleotide application was different even though cells isolated at E10.5 and E13.5 expressed very similar receptor mRNA profiles. They suggest that purinergic agonists carry potential for stimulating neurogenesis and enriching the contribution of dopaminergic neurons in vitro. Nucleotide receptor agonists may be of value for contributing to the formation and survival of dopaminergic neurons in vivo.

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Section: P2xmentioning

confidence: 99%

Nucleotides affect neurogenesis and dopaminergic differentiation of mouse fetal midbrain-derived neural precursor cells

Delic

Zimmermann

2010

Purinergic Signalling

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“…In addition to the rapid neurotransmitter-like action of ATP in maintaining normal brain function, it has become evident that ATP can also act as a neurotrophic factor and an important mediator in triggering cellular responses to various neurotoxic conditions. Extracellular purines stimulate the synthesis and release of protein trophic factors by astrocytes (Neary et al, 2004;Rathbone et al, 1999), and ATP can act in combination with these factors to regulate differentiation, neurite outgrowth, neurogenesis, and neurite regeneration of various neurons, including hippocampal primary cultures and slice cultures (Belliveau et al, 2006;D'Ambrosi et al, 2001;Heine et al, 2006;Lin et al, 2007). In addition, ATP acts on P2 receptors to inhibit presynaptic release of the cytotoxic excitatory neurotransmitter glutamate and stimulates release of the inhibitory neurotransmitter GABA from hippocampal nerves, thus serving a protective role against excitotoxicity induced by glutamate (Inoue et al, 1999).…”

Section: Adenosinementioning

confidence: 99%

P2Y₁ receptor signaling enhances neuroprotection by astrocytes against oxidative stress via IL‐6 release in hippocampal cultures

Fujita

Tozaki‐Saitoh

Inoue

2008

Glia

103

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Cell survival is a critical issue in the onset and progression of neurodegenerative diseases and following pathological events including ischemia and traumatic brain injury. Oxidative stress is the main cause of cell damage in such pathological conditions. Here, we report that adenosine 5'-triphosphate (ATP) protects hippocampal astrocytes from hydrogen peroxide (H(2)O(2))-evoked oxidative injury in astrocyte monocultures. The effect of ATP was prevented by a selective antagonist of or siRNAs against P2Y(1)R. Interestingly, in astrocyte-neuron cocultures, ATP also produced neuroprotective effects against H(2)O(2)-evoked neuronal cell death, whereas ATP did not produce any neuroprotective effects in monocultures. The ATP-induced neuroprotection in cocultures was completely inhibited by silencing of astrocytic P2Y(1)R expression, indicating that ATP acts on astrocytes and enhances their neuroprotective functions by activating P2Y(1)R. Furthermore, this neuroprotective effect was mimicked by applying conditioned medium from astrocytes that had been stimulated by ATP, implying an involvement of diffusible factors from astrocytes. We found that, in both purified astrocyte cultures and astrocyte-neuronal cocultures, ATP and the P2Y(1)R agonist 2-methylthioadenosine 5' diphosphate (2MeSADP) induced the release of interleukin-6 (IL-6), but this did not occur in neuron monocultures. Moreover, exogenous IL-6 produced a neuroprotective effect, and the neuroprotection induced by P2Y(1)R-stimulated astrocytes was prevented in the presence of an anti-IL-6 antibody. Taken together, these results suggest that P2Y(1)R-stimulated astrocytes protect against neuronal damage induced by oxidative stress, and that IL-6 is a crucial signaling molecule released from astrocytes. Thus, activation of P2Y(1)R in astrocytes may rescue neurons from secondary cell death under pathological conditions.

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“…This effect involved an increased sensitivity towards NGF due to the phosphorylation of TrkA and early response kinases (ERKs) [11]. P2 receptor activation was also reported to promote fiber outgrowth in the developing hippocampus [78], but it remained elusive whether this effect was mediated by P2X or P2Y receptors. In addition, extracellular ATP may influence neurite outgrowth in hippocampal neurons by modulating the adhesion mediated by neuronal cell adhesion molecules [173].…”

Section: Regulation Of Neurodegeneration and Regenerationmentioning

confidence: 99%

Functions of neuronal P2Y receptors

Hussl

Boehm

2006

Pflugers Arch - Eur J Physiol

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Within the last 15 years, at least eight different G protein-coupled nucleotide receptors, i.e., P2Y receptors, have been characterized by molecular means. While ionotropic P2X receptors are mainly involved in fast synaptic neurotransmission, P2Y receptors rather mediate slower neuromodulatory effects. This P2Y receptor-dependent neuromodulation relies on changes in synaptic transmission via either pre- or postsynaptic sites of action. At both sites, the regulation of voltage-gated or transmitter-gated ion channels via G protein-linked signaling cascades has been identified as the predominant underlying mechanisms. In addition, neuronal P2Y receptors have been found to be involved in neurotoxic and neurotrophic effects of extracellular adenosine 5-triphosphate. This review provides an overview of the most prominent actions mediated by neuronal P2Y receptors and describes the signaling cascades involved.

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P2 receptor-stimulation influences axonal outgrowth in the developing hippocampus in vitro

Cited by 40 publications

References 65 publications

Nucleotides affect neurogenesis and dopaminergic differentiation of mouse fetal midbrain-derived neural precursor cells

Nucleotides affect neurogenesis and dopaminergic differentiation of mouse fetal midbrain-derived neural precursor cells

P2Y₁ receptor signaling enhances neuroprotection by astrocytes against oxidative stress via IL‐6 release in hippocampal cultures

Functions of neuronal P2Y receptors

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P2 receptor-stimulation influences axonal outgrowth in the developing hippocampus in vitro

Cited by 40 publications

References 65 publications

Nucleotides affect neurogenesis and dopaminergic differentiation of mouse fetal midbrain-derived neural precursor cells

Nucleotides affect neurogenesis and dopaminergic differentiation of mouse fetal midbrain-derived neural precursor cells

P2Y1 receptor signaling enhances neuroprotection by astrocytes against oxidative stress via IL‐6 release in hippocampal cultures

Functions of neuronal P2Y receptors

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P2Y₁ receptor signaling enhances neuroprotection by astrocytes against oxidative stress via IL‐6 release in hippocampal cultures