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Neonatal proinflammatory stress induces accumulation of corticosterone and interleukin-6 in the hippocampus of juvenile rats: Potential mechanism of synaptic plasticity impairments

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Abstract

Infectious diseases in early postnatal ontogenesis can induce neuroinflammation, disrupt normal central nervous system development, and contribute to pathogenesis of cerebral pathologies in adults. To study long-term consequences of such early stress, we induced neonatal proinflammatory stress (NPS) by injecting bacterial lipopolysaccharide into rat pups on postnatal days 3 and 5 and then assessed the levels of corticosterone, proinflammatory cytokines and their mRNAs, and neurotrophins and their mRNAs in the hippocampus and neocortex of the one-month-old animals. Long-term potentiation (LTP) was studied in hippocampal slices as an index of synaptic plasticity. NPS-induced impairments of LTP were accompanied by the accumulation of corticosterone and IL-6 in the hippocampus. In the neocortex, a decrease in exon IV BDNF mRNA was detected. We suggest that excessive corticosterone delivery to hippocampal receptors and proinflammatory changes persisting during brain maturation are among the principal molecular mechanisms responsible for NPSinduced neuroplasticity impairments.

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Abbreviations

BDNF:

brain-derived neurotrophic factor

CNS:

central nervous system

CS:

corticosterone

GR:

glucocorticoid receptor

HPA:

hypothalamic–pituitary–adrenal axis

IL:

interleukin

LPS:

lipopolysaccharide

LTP:

long-term potentiation

MR:

mineralocorticoid receptor

NGF:

nerve growth factor

NPS:

neonatal proinflammatory stress

TNF:

tumor necrosis factor

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Authors and Affiliations

  1. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485, Moscow, Russia

    M. V. Onufriev, S. V. Freiman, D. I. Peregud, I. V. Kudryashova, A. O. Tishkina, M. Yu. Stepanichev & N. V. Gulyaeva

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  1. M. V. Onufriev
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  2. S. V. Freiman
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  3. D. I. Peregud
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  4. I. V. Kudryashova
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  5. A. O. Tishkina
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  6. M. Yu. Stepanichev
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  7. N. V. Gulyaeva
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Correspondence to M. V. Onufriev.

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Original Russian Text © M. V. Onufriev, S. V. Freiman, D. I. Peregud, I. V. Kudryashova, A. O. Tishkina, M. Yu. Stepanichev, N. V. Gulyaeva, 2017, published in Biokhimiya, 2017, Vol. 82, No. 3, pp. 410-417.

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Onufriev, M.V., Freiman, S.V., Peregud, D.I. et al. Neonatal proinflammatory stress induces accumulation of corticosterone and interleukin-6 in the hippocampus of juvenile rats: Potential mechanism of synaptic plasticity impairments. Biochemistry Moscow 82, 275–281 (2017). https://doi.org/10.1134/S0006297917030051

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  • DOI: https://doi.org/10.1134/S0006297917030051

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