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Nicotinamide prevents the long-term effects of perinatal asphyxia on apoptosis, non-spatial working memory and anxiety in rats

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Abstract

There is no established treatment for the long-term effects produced by perinatal asphyxia. Thus, we investigated the neuroprotection provided by nicotinamide against the effects elicited by perinatal asphyxia on hippocampus and behaviour observed at 30–90 days of age. Asphyxia was induced by immersing foetuses-containing uterine horns, removed from ready-to-deliver rats into a water bath at 37°C for 20 min. Caesarean-delivered siblings were used as controls. Saline or nicotinamide (0.8 mmol/kg, i.p.) was administered to control and asphyxia-exposed animals 24, 48, and 72 h after birth. The animals were examined for morphological changes in hippocampus, focusing on delayed cell death and mossy fibre sprouting, and behaviour, focusing on cognitive behaviour and anxiety. At the age of 30–45 days, asphyxia-exposed rats displayed (1) increased apoptosis, assessed in whole hippocampus by nuclear Hoechst staining, and (2) increased mossy fibre sprouting, restricted to the stratum oriens of dorsal hippocampus, assessed by Timm’s staining. Rats from the same cohorts displayed (3) deficits in non-spatial working memory, assessed by a novel object recognition task, and (4) increased anxiety, assessed by an elevated plus-maze test when examined at the age of 90 days. Nicotinamide prevented the effects elicited by perinatal asphyxia on apoptosis, working memory, and anxiety.

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Abbreviations

AS:

Asphyxia saline

AN:

Asphyxia nicotinamide

CA:

Cornus amonnis

CN:

Caesarean-delivered nicotinamide

CNS:

Central nervous system

CS:

Caesarean-delivered saline

DG:

Dentate gyrus

IML:

Inner molecular layer

MFS:

Mossy fibre sprouting

n.s.:

Non-significant

OML:

Outer molecular layer

P:

Postnatal day

PARP-1:

Poly(ADP-ribose) polymerase-1

PBS:

Phosphate buffered saline

S1, S2:

Session 1, 2

SEM:

Standard error of the mean

SL:

Stratum lucidum

SO:

Stratum oriens

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Acknowledgments

Contract Grant sponsors: FONDECYT (contract Grant numbers 1080447; 11070192) (MH-M, PM, DB); Regione Autonoma della Sardegna for Scientific Cooperation between Italy and Chile (Italy) (contract Grant number LR 19/96; 2003) (MM, MH-M); Atlantic Innovation Fund (Canada) (contract Grant number: 181780) (RAT); International Programme for Scientific cooperation CONICYT/DAAD (number 186-06-2006) (MH-M, PJG-H); NGFN + (BMBF)-TP9-Germany (PJG-H). The excellent technical and secretarial help from Mr. Juan Santibañez, Ms. Carmen Almeyda and Ms. Ana Maria Mendez is kindly acknowledged.

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Authors and Affiliations

  1. Programme of Molecular and Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, PO Box 70,000, Santiago 7, Chile

    Paola Morales, Diego Bustamante, Francisco Lisboa & Mario Herrera-Marschitz

  2. Department of Toxicology, Center of Excellence on Neurobiology of Dependence, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy

    Nicola Simola & Micaela Morelli

  3. Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PEI, C1A4P3, Canada

    R. Andrew Tasker

  4. Department of Biochemistry and Molecular Biology, Chemical and Pharmaceutical Sciences Faculty, University of Chile, Santiago, Chile

    Jenny Fiedler

  5. Department of Psychopharmacology J 5, Central Institute for Mental Health, 68159, Mannheim, Germany

    Peter J. Gebicke-Haerter

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  1. Paola Morales
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  2. Nicola Simola
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  3. Diego Bustamante
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  4. Francisco Lisboa
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  6. Peter J. Gebicke-Haerter
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  7. Micaela Morelli
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  9. Mario Herrera-Marschitz
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Corresponding author

Correspondence to Mario Herrera-Marschitz.

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P. Morales and N. Simola contributed equally to this work.

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Morales, P., Simola, N., Bustamante, D. et al. Nicotinamide prevents the long-term effects of perinatal asphyxia on apoptosis, non-spatial working memory and anxiety in rats. Exp Brain Res 202, 1–14 (2010). https://doi.org/10.1007/s00221-009-2103-z

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  • DOI: https://doi.org/10.1007/s00221-009-2103-z

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