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Verfasst von:Corcoran, Alan [VerfasserIn]   i
 Kunze, Reiner [VerfasserIn]   i
 Harney, Sarah C. [VerfasserIn]   i
 Breier, Georg [VerfasserIn]   i
 Marti, Hugo [VerfasserIn]   i
 O'Connor, John J. [VerfasserIn]   i
Titel:A role for prolyl hydroxylase domain proteins in hippocampal synaptic plasticity
Verf.angabe:Alan Corcoran, Reiner Kunze, Sarah C. Harney, Georg Breier, Hugo H. Marti, and John J. O'Connor
E-Jahr:2013
Jahr:15 May 2013
Umfang:12 S.
Teil:volume:23
 year:2013
 number:10
 pages:861-872
 extent:12
Fussnoten:Gesehen am 12.05.2021
Titel Quelle:Enthalten in: Hippocampus
Ort Quelle:New York, NY [u.a.] : Wiley, 1991
Jahr Quelle:2013
Band/Heft Quelle:23(2013), 10, Seite 861-872
ISSN Quelle:1098-1063
Abstract:Hypoxia-inducible factors (HIFs) are key transcriptional regulators that play a major role in oxygen homeostasis. HIF activity is tightly regulated by oxygen-dependent hydroxylases, which additionally require iron and 2-oxoglutarate as cofactors. Inhibition of these enzymes has become a novel target to modulate the hypoxic response for therapeutic benefit. Inhibition of prolyl-4-hydroxylase domains (PHDs) have been shown to delay neuronal cell death and protect against ischemic injury in the hippocampus. In this study we have examined the effects of prolyl hydroxylase inhibition on synaptic transmission and plasticity in the hippocampus. Field excitatory postsynaptic potentials (fEPSPs) and excitatory postsynaptic currents (EPSCs) were elicited by stimulation of the Schaffer collateral pathway in the CA1 region of the hippocampus. Treatment of rat hippocampal slices with low concentrations (10 µM) of the iron chelator deferosoxamine (DFO) or the 2-oxoglutarate analogue dimethyloxalyl glycine (DMOG) had no effect on fEPSP. In contrast, application of 1 mM DMOG resulted in a significant decrease in fEPSP slope. Antagonism of the NMDA receptor attenuated the effects of DMOG on baseline synaptic signalling. In rat hippocampal slices pretreated with DMOG and DFO the induction of long-term potentiation (LTP) by tetanic stimulation was strongly impaired. Similarly, neuronal knockout of the single PHD family member PHD2 prevented murine hippocampal LTP. Preconditioning of PHD2 deficient hippocampi with either DMOG, DFO, or the PHD specific inhibitor JNJ-42041935, did not further decrease LTP suggesting that DMOG and DFO influences synaptic plasticity primarily by inhibiting PHDs rather than unspecific effects. These findings provide striking evidence for a modulatory role of PHD proteins on synaptic plasticity in the hippocampus. © 2013 Wiley Periodicals, Inc.
DOI:doi:10.1002/hipo.22142
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/https://doi.org/10.1002/hipo.22142
 Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/hipo.22142
 DOI: https://doi.org/10.1002/hipo.22142
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:dimethyloxalyl glycine
 HIF-1alpha
 hippocampus
 hypoxia
 long-term potentiation
 prolyl hydroxylase domain
K10plus-PPN:1757708413
Verknüpfungen:→ Zeitschrift

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