Social adversity during juvenile age but not adulthood increases susceptibility to an immune challenge later in life

1. Neurobiol Stress. 2023 Feb 8;23:100526. doi: 10.1016/j.ynstr.2023.100526.
eCollection 2023 Mar.

Social adversity during juvenile age but not adulthood increases susceptibility
to an immune challenge later in life.

Guerrin CGJ(1), Doorduin J(1), Prasad K(1), Vazquez-Matias DA(1), Barazzuol
L(2)(3), de Vries EFJ(1).

Author information:
(1)Department of Nuclear Medicine and Molecular Imaging, University Medical
Center Groningen, University of Groningen, Hanzeplein 1, 9713, GZ, Groningen,
the Netherlands.
(2)Department of Radiation Oncology, University of Groningen, University Medical
Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
(3)Department of Biomedical Sciences of Cells and Systems, University of
Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ,
Groningen, the Netherlands.

Adverse experiences in early life can increase mental vulnerability to immune
challenges experienced later in life, which may induce the development of
stress-related psychopathologies. Here, we investigated whether the combined
effect of both events is higher if the first adverse experience occurs when the
brain is still in development. Therefore, male Wistar rats were exposed to
repeated social defeat (RSD, first hit) during juvenile age or adulthood and to
an immune challenge consisting of a single injection of lipopolysaccharide (LPS,
second hit) in adulthood. Control animals were not exposed to RSD, but only to
the LPS challenge. Translocator protein density, a marker for reactive
microglia, microglia cell density and plasma corticosterone levels were measured
using in vivo [11C]PBR28 positron emission tomography, iba1 immunostaining, and
corticosterone ELISA, respectively. Anhedonia, social behavior and anxiety were
measured with the sucrose preference, social interaction, and open field tests,
respectively. Rats exposed to RSD during juvenile age exhibited enhanced
anhedonia and social interaction dysfunction after an immune challenge in
adulthood. This enhanced susceptibility was not observed in rats exposed to RSD
during adulthood. In addition, exposure to RSD synergistically increased
microglia cell density and glial reactivity to the LPS challenge. This increase
in microglia cell density and reactivity to the LPS challenge was more
pronounced in rats exposed to RSD during juvenile age than in adulthood.
Exposure to RSD alone in juvenile age or adulthood induced similar short-term
anhedonia, a long-lasting increase in plasma corticosterone and microglial
activity, but no change in anxiety and social behavior. Our findings indicate
that exposure to social stress during juvenile age, but not adulthood, primes
the immune system and increases the sensitivity to an immune challenge
experienced later in life. This suggests that juvenile social stress can have
more deleterious effects in the long term than similar stress in adulthood.

© 2023 The Authors.

DOI: 10.1016/j.ynstr.2023.100526
PMCID: PMC9945751
PMID: 36844420

Conflict of interest statement: The authors declare that they have no known
competing financial interests or personal relationships that could have appeared
to influence the work reported in this paper.

Auteurs Bordeaux Neurocampus