Molecular, Cellular, and Behavioural Effects Produced by Perinatal Asphyxia: Protection by Poly (ADP-Ribose) Polymerase 1 (PARP-1) Inhibition View Full Text


Ontology type: schema:Chapter     


Chapter Info

DATE

2014

AUTHORS

T. Neira-Peña , P. Espina-Marchant , E. Rojas-Mancilla , D. Esmar , C. Kraus , V. Munoz , R. Perez , B. Rivera , D. Bustamante , J. L. Valdes , M. Hermoso , P. Gebicke-Haerter , P. Morales , M. Herrera-Marschitz

ABSTRACT

Perinatal asphyxia implies oxygen interruption at birth, leading to death whenever reoxygenation is not promptly reestablished. Reoxygenation triggers a cascade of biochemical events for restoring function at the cost of improper homeostasis. The effects observed long after perinatal asphyxia have been explained by overexpression of sentinel proteins, such as poly(ADP-ribose) polymerase 1 (PARP-1), competing for NAD+ during reoxygenation, leading to the idea that sentinel protein inhibition constitutes a suitable therapeutic strategy. Asphyxia also induces transcriptional activation of proinflammatory factors, including NFκB, and its subunit p65, whose translocation to the nucleus was found here, is significantly increased in brain tissue from asphyxia-exposed animals, in tandem with PARP-1 overactivation, suggesting that PARP-1 inhibition downregulates the expression of proinflammatory cytokines. Indeed, TNF-α and IL-1β were found to be increased 8 and 24 h after perinatal asphyxia in mesencephalon and hippocampus of rat neonates. The possible neuroprotection effect of nicotinamide has been studied in an experimental model of global perinatal asphyxia in rats, inducing the insult by immersing rat fetuses into a water bath for various periods of time. Following asphyxia, the pups are delivered, immediately treated, or given to surrogate dams for nursing, pending further experiments. Systemic administration of nicotinamide was found to rapidly distribute into the brain reaching a steady-state concentration sufficient to inhibit PARP-1 activity for several hours. Nicotinamide prevented several of the long-term consequences elicited by perinatal asphyxia, supporting the idea that it constitutes a lead for exploring compounds with similar or better pharmacological profiles. More... »

PAGES

2075-2098

References to SciGraph publications

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  • Book

    TITLE

    Handbook of Neurotoxicity

    ISBN

    978-1-4614-5835-7
    978-1-4614-5836-4

    Author Affiliations

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/978-1-4614-5836-4_115

    DOI

    http://dx.doi.org/10.1007/978-1-4614-5836-4_115

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1041982255


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