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J Immunol. 2019 Feb 8. pii: ji1801351. doi: 10.4049/jimmunol.1801351. [Epub ahead of print]

Programming Effects of Pubertal Lipopolysaccharide Treatment in Male and Female CD-1 Mice.

Author information

1
School of Psychology, Faculty of Social Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
2
MD Program, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
3
Department of Psychology, College of Social and Applied Human Sciences, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
4
School of Bioscience, Faculty of Science, Cardiff University, Cardiff CF10 3AX, United Kingdom.
5
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
6
Department of Nutrition, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada; and.
7
Department of Psychological and Brain Sciences, College of Arts and Sciences, University of Delaware, Newark, DE 19716.
8
School of Psychology, Faculty of Social Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada; nafissa.ismail@uottawa.ca.

Abstract

Puberty is a critical period of development marked by sexual, immune, and neural maturation. Exposure to stress during this period can lead to enduring changes in brain functioning and in behavior; however, the underlying mechanisms and the programming effects of stress during puberty remain unknown. Therefore, the objective of this study was to investigate the programming effects of pubertal immune challenge in response to a homotypic stressor later in life in CD-1 mice. Age and sex differences in the peripheral and central cytokine levels, along with sickness behavior and telemetry data, were analyzed following the secondary treatment. The results showed that pretreatment with LPS attenuated the immune response to a second homotypic challenge. Males pretreated with LPS during puberty and in early adulthood displayed an attenuated hypothermic response following the second LPS treatment compared with saline-pretreated controls, which is consistent with the attenuated peripheral IL-6 and IFN-γ concentrations. Females pretreated with LPS during puberty displayed lower IL-1β, TNF-α, and IL-6 mRNA expression in the prefrontal cortex following the secondary immune challenge compared with saline controls. The results of this study show that exposure to LPS during puberty programs the peripheral and central immune responses, resulting in an attenuated immune response following a subsequent homotypic stressor. Thus, exposure to an immune challenge during puberty affects immune function later in life, which could permanently affect brain function and have implications on mental health.

PMID:
30737275
DOI:
10.4049/jimmunol.1801351

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