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Developmental changes in expression levels of the chosen subunits of NMDA and AMPA receptors and action of their antagonists on physiological and epileptic phenomena
Szczurowska, Ewa Katarzyna ; Mareš, Pavel (advisor) ; Rokyta, Richard (referee) ; Bendová, Zdeňka (referee)
During early stages of postnatal development, glutamate receptors of NMDA and AMPA type, undergo intensive functional changes due to modifications of their subunit composition (Pachernegg et al., 2012: Paoletti et al., 2013). The NR2B-containing NMDARs (NR2B/NMDARs) and GluA2-lacking AMPARs (Ca 2+ -permeable) that are highly expressed in immature brain, are implicated in increased excitability, seizures generation, excitotoxicity, and neuronal death (Vizi et al., 2013). Pharmacological blockade of these types of receptors by their specific antagonists, can exhibit anticonvulsant effects at early stages of postnatal development. Therefore, we tested the influence of the IEM1460, a specific antagonist of Ca 2+ -permeable AMPARs and the Ro 25-6981 maleate, a highly selective and activity-dependent antagonist of NR2B/NMDARs on physiological excitability and epileptic phenomena induced in immature rats. Anticonvulsant action of IEM1460 was tested in two models of epileptic seizures: pentylenetetrazol (PTZ)- induced convulsions and cortical afterdischarges (ADs), induced in animals at P12, P18 and P25. Our results indicate that the effects of IEM1460 on various types of seizures depend on their sites of origin in the brain, developmental stage, and GluA2 subunit expression profile. To clarify the action...
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Developmental changes in expression levels of the chosen subunits of NMDA and AMPA receptors and action of their antagonists on physiological and epileptic phenomena
Szczurowska, Ewa Katarzyna ; Mareš, Pavel (advisor) ; Rokyta, Richard (referee) ; Bendová, Zdeňka (referee)
During early stages of postnatal development, glutamate receptors of NMDA and AMPA type, undergo intensive functional changes due to modifications of their subunit composition (Pachernegg et al., 2012: Paoletti et al., 2013). The NR2B-containing NMDARs (NR2B/NMDARs) and GluA2-lacking AMPARs (Ca 2+ -permeable) that are highly expressed in immature brain, are implicated in increased excitability, seizures generation, excitotoxicity, and neuronal death (Vizi et al., 2013). Pharmacological blockade of these types of receptors by their specific antagonists, can exhibit anticonvulsant effects at early stages of postnatal development. Therefore, we tested the influence of the IEM1460, a specific antagonist of Ca 2+ -permeable AMPARs and the Ro 25-6981 maleate, a highly selective and activity-dependent antagonist of NR2B/NMDARs on physiological excitability and epileptic phenomena induced in immature rats. Anticonvulsant action of IEM1460 was tested in two models of epileptic seizures: pentylenetetrazol (PTZ)- induced convulsions and cortical afterdischarges (ADs), induced in animals at P12, P18 and P25. Our results indicate that the effects of IEM1460 on various types of seizures depend on their sites of origin in the brain, developmental stage, and GluA2 subunit expression profile. To clarify the action...
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