“…However, this stimulation-evoked release of ATP from nerve terminals seems to differ from the release of classical neurotransmitters (Farinas et al, 1992;Magalhães-Cardoso et al, 2003;Rabasseda et al, 1987;Santos et al, 1999; see also Coco et al, 2003). In particular, this release of ATP is disproportionally larger at higher frequencies of nerve stimulation (Cunha et al, 1996a;Wieraszko et al, 1989). We have recently confirmed that this release of ATP from hippocampal nerve terminals required greater intensities of stimulation than these required to trigger the release of glutamate, GABA or acetylcholine and also involves the recruitment of L-type calcium channels rather than N-or Ptype calcium channels (Rodrigues et al, 2004).…”
Section: Adenosine As a Synaptic Modulator-a 2a Receptorsmentioning
Adenosine is a prototypical neuromodulator, which mainly controls excitatory transmission through the activation of widespread inhibitory A 1 receptors and synaptically located A 2A receptors. It was long thought that the predominant A 1 receptor-meditated modulation by endogenous adenosine was a homeostatic process intrinsic to the synapse. New studies indicate that endogenous extracellular adenosine is originated as a consequence of the release of gliotransmitters, namely ATP, which sets a global inhibitory tonus in brain circuits rather than in a single synapse. Thus, this neuron-glia long-range communication can be viewed as a form of non-synaptic transmission (a concept introduced by Professor Sylvester Vizi), designed to reduce noise in a circuit. This neuron-glia-induced adenosine release is also responsible for exacerbating salient information through A 1 receptor-mediated heterosynaptic depression, whereby the activation of a particular synapse recruits a neuron-glia network to generate extracellular adenosine that inhibits neighbouring non-tetanised synapses. In parallel, the local activation of facilitatory A 2A receptors by adenosine, formed from ATP released only at high frequencies from neuronal vesicles, down-regulates A 1 receptors and facilitates plasticity selectively in the tetanised synapse. Thus, upon high-frequency firing of a given pathway, the combined exacerbation of global A 1 receptormediated inhibition in the circuit (heterosynaptic depression) with the local synaptic activation of A 2A receptors in the activated synapse, cooperate to maximise salience between the activated and non-tetanised synapses. #
“…However, this stimulation-evoked release of ATP from nerve terminals seems to differ from the release of classical neurotransmitters (Farinas et al, 1992;Magalhães-Cardoso et al, 2003;Rabasseda et al, 1987;Santos et al, 1999; see also Coco et al, 2003). In particular, this release of ATP is disproportionally larger at higher frequencies of nerve stimulation (Cunha et al, 1996a;Wieraszko et al, 1989). We have recently confirmed that this release of ATP from hippocampal nerve terminals required greater intensities of stimulation than these required to trigger the release of glutamate, GABA or acetylcholine and also involves the recruitment of L-type calcium channels rather than N-or Ptype calcium channels (Rodrigues et al, 2004).…”
Section: Adenosine As a Synaptic Modulator-a 2a Receptorsmentioning
Adenosine is a prototypical neuromodulator, which mainly controls excitatory transmission through the activation of widespread inhibitory A 1 receptors and synaptically located A 2A receptors. It was long thought that the predominant A 1 receptor-meditated modulation by endogenous adenosine was a homeostatic process intrinsic to the synapse. New studies indicate that endogenous extracellular adenosine is originated as a consequence of the release of gliotransmitters, namely ATP, which sets a global inhibitory tonus in brain circuits rather than in a single synapse. Thus, this neuron-glia long-range communication can be viewed as a form of non-synaptic transmission (a concept introduced by Professor Sylvester Vizi), designed to reduce noise in a circuit. This neuron-glia-induced adenosine release is also responsible for exacerbating salient information through A 1 receptor-mediated heterosynaptic depression, whereby the activation of a particular synapse recruits a neuron-glia network to generate extracellular adenosine that inhibits neighbouring non-tetanised synapses. In parallel, the local activation of facilitatory A 2A receptors by adenosine, formed from ATP released only at high frequencies from neuronal vesicles, down-regulates A 1 receptors and facilitates plasticity selectively in the tetanised synapse. Thus, upon high-frequency firing of a given pathway, the combined exacerbation of global A 1 receptormediated inhibition in the circuit (heterosynaptic depression) with the local synaptic activation of A 2A receptors in the activated synapse, cooperate to maximise salience between the activated and non-tetanised synapses. #
“…Thus, ATP is stored in synaptic vesicles and nerve terminals release ATP on stimulation (reviewed in [110]). This release of ATP is larger the higher the frequency of nerve stimulation [111,112] and the contribution of ATP-derived adenosine increases with increasing frequencies of nerve stimulation [112,113]. In contrast, the contribution of adenosine released as such through equilibrative nucleoside transporters predominates at lower frequencies of nerve stimulation ( [112]; see also [114]).…”
Section: Generation Of Extracellular Adenosinementioning
Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A 1 receptors (A 1 Rs) and the less abundant, but widespread, facilitatory A 2A Rs. It is commonly assumed that A 1 Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A 1 R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A 1 Rs in chronic noxious situations. In contrast, A 2A Rs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A 2A R antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A 2A R antagonists as novel protective agents in neurodegenerative diseases such as Parkinson's and Alzheimer's disease, ischemic brain damage and epilepsy. The greater interest of A 2A R blockade compared to A 1 R activation does not mean that A 1 R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A 2A R antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A 1 Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different.Abbreviations: Ab -b-amyloid peptide; A 1 Rs -A 1 receptors; A 2A Rs -A 2A
“…ATP released from astrocytes diffused on the SW-CNT network, which means the released ATP and SW-CNT network interact by interaction (Figure 3) [54]. 10.1080/20022727.2017.1323853-F0003Figure 3.Illustration of active interaction region of CNTs through released ATP binding to CNT.Released ATP from astrocytes diffused on the SW-CNT network, which means released ATP and the SW-CNT network interact by interaction. Purinergic signaling is included in nervous regeneration following epilepsy-associated seizures in the brain [55], ischemia and neurodegenerative disorders [56]. Moreover, ATP can stimulate astrocyte proliferation, which contributes to hyperplastic responses, and P2Y receptor antagonists have been proposed as potential neuroprotective agents in the cortex.…”
Section: Cnts Can Produce An Active Interaction Region Between Triggementioning
Introduction: Functionalised carbon nanotubes (CNTs) have been shown to be promising biomaterials in neural systems, such as CNT -based nerve scaffolds to drive nerve regeneration. CNTs have been shown to modulate neuronal growth and improve electrical conductivity of neurons.Methods: Cultured astrocytes on the functionalized CNTs (PEG, caroboxyl group) were assessed for distribution of GABA, glutamate uptake assay using isotope and change of conductance of CNTs by ATP. Immunostaining of GABA using anti-GABA (red), anti-GFAP (green) antibody in primary cortical astrocytes on MW-CNT and PDL coverslips.Results: The functionalization of CNTs has improved their solubility and biocompatibility and alters their cellular interaction pathways. Recently, CNTs have been shown to modulate morphofunctional characteristics of glia as well as neurons. Among the various types of glia, astrocytes express diverse receptors for corresponding neurotransmitters and release gliotransmitters, including glutamate, adenosine triphosphate, and γ-amino butyric acid. Gliotransmitters are primarily released from astrocytes and play important roles in glia–neuron crosstalk.Conclusion: This review focuses on the effects of CNTs on glial cells and discusses how functionalized CNTs can modulate morphology and gliotransmitters of glial cells. Based on exciting new findings, they look to be a promising material for use in brain disease therapy or neuroprosthetics.
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