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Acute and Chronic Lipopolysaccharide-Induced Stress Changes Expression of Proinflammatory Cytokine Genes in the Rat Brain Region-Specifically and Affects Learning and Memory

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Abstract

Goal of the current work was to conduct comparative analysis of the effects of acute and chronic lipopolysaccharide-induced stress on the behavior of rats in the Morris water maze test and on expression of mRNA of proinflammatory cytokines and BDNF in different brain structures. Relevance of this study is related to poor understanding of the effects of acute and chronic stress on manifestation of cognitive brain functions, as well as ambiguity of the literature data on the effects of both stresses on hypothalamic pituitary axis and expression of the proinflammatory cytokine genes. In the experiments with rats, acute lipopolysaccharide (LPS)-induced stress improved learning in the Morris water maze. For the period of learning, the rats under acute stress swam on average less distance to reach a hidden platform, spent less time in the peripheral zone of the pool (thigmotaxis), and had low speed compared to the control animals and to the group of rats under chronic LPS-induced stress. In the test without a platform in the pool there were no significant differences between the groups on the time spent in the platform quadrant and distance swum. Acute stress caused substantial increase of the TNF-α and IL-1β mRNA concentrations in the hippocampus and amygdala, but not in the frontal lobe in comparison with the control animals. Although chronic stress increased the levels of the TNF-α and IL-1β mRNA in the amygdala and hippocampus compared to the control groups, significance between the groups was only marginal and BDNF concentration did not differ from the control animals in any of the brain structures mentioned. Expression of the IL-6 mRNA only marginally increased in the amygdala of the animals under the acute LPS-induced stress and marginally decreased in the animals under chronic LPS stress in the hippocampus relative to the control groups. In total, the most pronounced molecular-biochemical changes occurred in the amygdala and hippocampus, where increase of the expression of the TNF-α and IL-1β interleukins mRNAs were observed in the animals under acute and chronic LPS-induced stress and no changes in the BDNF mRNA concentration were observed in the frontal lobe.

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Abbreviations

BDNF:

brain-derived neurotrophic factor

LPS:

lipopolysaccharide

LPS-O:

administration of a single dose of LPS 1 h prior to the start of training

LPS-X:

administration of LPS for investigation of the effect of chronic stress

PBS:

phosphate-buffered saline

PBS-O:

administration of a single dose of PBS 1 h prior to the start of learning

PBS-X:

administration of PBS for investigation of the effect of chronic stress

TNF-α:

tumor necrosis factor alpha

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Funding

This work was financially supported by the Russian Foundation for Basic Research, grant no. 19-015-00129 A.

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Authors and Affiliations

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

    Mariya I. Zaichenko, Pavel Philenko, Viktoriya Sidorina & Grigory A. Grigoryan

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  1. Mariya I. Zaichenko
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  2. Pavel Philenko
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  3. Viktoriya Sidorina
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  4. Grigory A. Grigoryan
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Contributions

Zaichenko, M.I. – supervision of experimental work, participation in performing experiments and discussion of the results; Philenko, P. – performing biochemical experiments; Sidorina, V. – performing behavioral experiments; Grigoryan, G.A. – analysis of the literature and of obtained results, writing the paper.

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Correspondence to Mariya I. Zaichenko.

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The authors declare no conflict of interest in financial or any other sphere. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Zaichenko, M.I., Philenko, P., Sidorina, V. et al. Acute and Chronic Lipopolysaccharide-Induced Stress Changes Expression of Proinflammatory Cytokine Genes in the Rat Brain Region-Specifically and Affects Learning and Memory. Biochemistry Moscow 88, 526–538 (2023). https://doi.org/10.1134/S0006297923040089

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