The hippocampus is comprised of two distinct subfields that show different responses to hypoxic/ischemic brain injury: the CA1 region is particularly susceptible, whereas the dentate gyrus (DG) is quite resistant. A major resistance of the DG to ischemia in adulthood is probably due to the regenerative capacity of the neural stem cells of the subgranular zone (SGZ) that proliferate and maturate into neurons, astrocytes and oligodendrocytes in response to multiple factors, including ischemic injury. The synaptic and proliferative response of the DG to severe oxygen and glucose deprivation (OGD) in acute rat hippocampal slices and the contribution of P1 and P2 purinergic receptors to these phenomena was investigated. Nine min OGD always induced the appearance of anoxic depolarization (AD), a clear sign of tissue damage, and the irreversible block of synaptic activity up to 24 hours from the end of the insult, as assessed by extracellular recordings of field excitatory post-synaptic potentials (fEPSPs) in the dentate molecular layer of the hippocampal slices. The selective antagonist of adenosine A2A receptors ZM241385, applied before and during OGD, prevented or delayed the appearance of AD and protected from the irreversible block of protected from the irreversible block of neurotransmission induced by the 9-min OGD. Similar effects were obtained in the presence of the selective antagonists of P2Y1 receptor MRS2179 and of P2X7 receptor BBG. In hippocampal slices prepared from bromodeoxyrudine (BrdU)-treated rats and incubated with the immature neuronal marker doublecortin (DCX), the number of BrdU+ cells of the SGZ was significantly decreased 6 hours after OGD, but returned to control values 24 hours thereafter, when a significant increase of DCX immunofluorescence was also observed. The decrease of the number of BrdU+ cells 6 hours after OGD was antagonized by ZM241385 and BBG, but not by MRS2179 that, 24 hours after OGD, reduced the number of BrdU+ cells. Data indicate that A2A, P2Y1 and P2X7 receptors contribute to the early damage induced by OGD in the DG likely contributing to glutamate induced excitotoxic effects that causes irreversible synaptic failure after severe OGD. A2A and P2X7 receptors are also involved in the decreased proliferation of immature neuronal cells at a precocious time after OGD. Neurotransmission induced by the 9-min OGD. Similar effects were obtained in the presence of the selective antagonists of P2Y1 receptor MRS2179 and of P2X7 receptor BBG. In hippocampal slices prepared from bromodeoxyrudine (BrdU)-treated rats and incubated with the immature neuronal marker doublecortin (DCX), the number of BrdU+ cells of the SGZ was significantly decreased 6 hours after OGD, but returned to control values 24 hours thereafter, when a significant increase of DCX immunofluorescence was also observed. The decrease of the number of BrdU+ cells 6 hours after OGD was antagonized by ZM241385 and BBG, but not by RS2179 that, 24 hours after OGD, reduced the number of BrdU+ cells. Data indicate that A2A, P2Y1 and P2X7 receptors contribute to the early damage induced by OGD in the DG likely contributing to glutamateinduced excitotoxic effects that causes irreversible synaptic failure after severe OGD. A2A and P2X7 receptors are also involved in the decreased proliferation of immature neuronal cells at a precocious time after OGD.

Role of P1 and P2 purinergic receptors in the dentate gyrus during in vitro ischemia / Pugliese, Am; Maraula, G; Lana, D; Fusco, I; Mello, T; Galli, A; Coppi, E; Pedata, F. - STAMPA. - (2015), pp. 49-49. (Intervento presentato al convegno 6th Joint German-Italian Purine Club Meeting, International conference on purinergic signalling tenutosi a Hamburg nel July, 23-25 2015).

Role of P1 and P2 purinergic receptors in the dentate gyrus during in vitro ischemia

PUGLIESE, ANNA MARIA;MARAULA, GIOVANNA;LANA, DANIELE;FUSCO, IRENE;MELLO, TOMMASO;Galli, A;COPPI, ELISABETTA;PEDATA, FELICITA
2015

Abstract

The hippocampus is comprised of two distinct subfields that show different responses to hypoxic/ischemic brain injury: the CA1 region is particularly susceptible, whereas the dentate gyrus (DG) is quite resistant. A major resistance of the DG to ischemia in adulthood is probably due to the regenerative capacity of the neural stem cells of the subgranular zone (SGZ) that proliferate and maturate into neurons, astrocytes and oligodendrocytes in response to multiple factors, including ischemic injury. The synaptic and proliferative response of the DG to severe oxygen and glucose deprivation (OGD) in acute rat hippocampal slices and the contribution of P1 and P2 purinergic receptors to these phenomena was investigated. Nine min OGD always induced the appearance of anoxic depolarization (AD), a clear sign of tissue damage, and the irreversible block of synaptic activity up to 24 hours from the end of the insult, as assessed by extracellular recordings of field excitatory post-synaptic potentials (fEPSPs) in the dentate molecular layer of the hippocampal slices. The selective antagonist of adenosine A2A receptors ZM241385, applied before and during OGD, prevented or delayed the appearance of AD and protected from the irreversible block of protected from the irreversible block of neurotransmission induced by the 9-min OGD. Similar effects were obtained in the presence of the selective antagonists of P2Y1 receptor MRS2179 and of P2X7 receptor BBG. In hippocampal slices prepared from bromodeoxyrudine (BrdU)-treated rats and incubated with the immature neuronal marker doublecortin (DCX), the number of BrdU+ cells of the SGZ was significantly decreased 6 hours after OGD, but returned to control values 24 hours thereafter, when a significant increase of DCX immunofluorescence was also observed. The decrease of the number of BrdU+ cells 6 hours after OGD was antagonized by ZM241385 and BBG, but not by MRS2179 that, 24 hours after OGD, reduced the number of BrdU+ cells. Data indicate that A2A, P2Y1 and P2X7 receptors contribute to the early damage induced by OGD in the DG likely contributing to glutamate induced excitotoxic effects that causes irreversible synaptic failure after severe OGD. A2A and P2X7 receptors are also involved in the decreased proliferation of immature neuronal cells at a precocious time after OGD. Neurotransmission induced by the 9-min OGD. Similar effects were obtained in the presence of the selective antagonists of P2Y1 receptor MRS2179 and of P2X7 receptor BBG. In hippocampal slices prepared from bromodeoxyrudine (BrdU)-treated rats and incubated with the immature neuronal marker doublecortin (DCX), the number of BrdU+ cells of the SGZ was significantly decreased 6 hours after OGD, but returned to control values 24 hours thereafter, when a significant increase of DCX immunofluorescence was also observed. The decrease of the number of BrdU+ cells 6 hours after OGD was antagonized by ZM241385 and BBG, but not by RS2179 that, 24 hours after OGD, reduced the number of BrdU+ cells. Data indicate that A2A, P2Y1 and P2X7 receptors contribute to the early damage induced by OGD in the DG likely contributing to glutamateinduced excitotoxic effects that causes irreversible synaptic failure after severe OGD. A2A and P2X7 receptors are also involved in the decreased proliferation of immature neuronal cells at a precocious time after OGD.
2015
6th Joint German-Italian Purine Club Meeting, Purines 2015
6th Joint German-Italian Purine Club Meeting, International conference on purinergic signalling
Hamburg
Pugliese, Am; Maraula, G; Lana, D; Fusco, I; Mello, T; Galli, A; Coppi, E; Pedata, F
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1012276
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