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Neonatal inflammation produces selective behavioural deficits and alters N-methyl-d-aspartate receptor subunit mRNA in the adult rat brain

Authors

  • E.-M. Harré,

    1. Hotchkiss Brain Institute and Institute of Infection, Immunity and Inflammation, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Health Sciences Centre, 3330 Hospital Drive NW, Calgary, Alberta, Canada, T2N 4N1
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    • *

      E.-M.H. and M.A.G. contributed equally to this work.

  • M. A. Galic,

    1. Hotchkiss Brain Institute and Institute of Infection, Immunity and Inflammation, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Health Sciences Centre, 3330 Hospital Drive NW, Calgary, Alberta, Canada, T2N 4N1
    2. Department of Medicine, University of Alberta, Edmonton, Alberta, Canada, T6G 2S2
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    • *

      E.-M.H. and M.A.G. contributed equally to this work.

  • A. Mouihate,

    1. Hotchkiss Brain Institute and Institute of Infection, Immunity and Inflammation, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Health Sciences Centre, 3330 Hospital Drive NW, Calgary, Alberta, Canada, T2N 4N1
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  • F. Noorbakhsh,

    1. Department of Medicine, University of Alberta, Edmonton, Alberta, Canada, T6G 2S2
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  • Q. J. Pittman

    1. Hotchkiss Brain Institute and Institute of Infection, Immunity and Inflammation, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Health Sciences Centre, 3330 Hospital Drive NW, Calgary, Alberta, Canada, T2N 4N1
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Errata

This article is corrected by:

  1. Errata: Neonatal inflammation produces selective behavioural deficits and alters N-methyl-d-aspartate receptor subunit mRNA in the adult rat brain Volume 27, Issue 8, 2210, Article first published online: 11 April 2008

M. A. Galic, 1Hotchkiss Brain Institute and Institute of Infection, Immunity and Inflammation, Department of Physiology and Biophysics, as above.
E-mail: magalic@ucalgary.ca

Abstract

Peripheral inflammation causes production of central cytokines that alter transmission at the N-methyl-d-aspartate receptor (NR). During development, NRs are important for synaptic plasticity and network connectivity. We therefore asked if neonatal inflammation would alter expression of NRs in the brain and behavioural performance in adulthood. We gave lipopolysaccharide (LPS) (100 µg/kg, i.p.) or saline to male rats on postnatal day (P)5, P14, P30 or P77. Subsequently we assessed mRNA levels of the NR1, NR2A, B, C and D subunits in the hippocampus and cortex either acutely (2 h) or in adulthood using real-time reverse transcriptase-polymerase chain reaction. We explored learning and memory behaviours in adult rats using the Morris water maze and contextual fear conditioning paradigms. Hippocampal NR1 mRNA was acutely increased in the P5- and P77-treated rats but was reduced in adults treated with LPS at P5, P30 and P77. P14 LPS-treated rats showed few acute changes but showed pronounced increases in NR2A, B, C and D subunit mRNA later in adulthood. The cortex displayed relatively few acute changes in expression in the neonatal-treated rats; however, it showed robust changes in NR2B, C and D mRNA in all groups given LPS in adulthood. Behavioural deficits were observed specifically in the P5 and P30 LPS-treated groups in the water maze probe trial and fear conditioning tests, consistent with hippocampal NR1 mRNA down-regulation. Thus, a single bout of inflammation during development can programme specific and persistent differences in NR mRNA subunit expression in the hippocampus, which could be associated with behavioural and cognitive deficits in adulthood.

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