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Cited by 30Neuroinflammation and Neurodegeneration MechanismsTryptophan and brain disordersStress Responses and Cortisol

The sex differences of the behavior response to early Life immune stimulation: Microglia and astrocytes involvement

Berkiks, I., Garcia-Segura, L.M., Nassiri, A., Mesfioui, A., Ouichou, A., Boulbaroud, S., Bahbiti, Y., Lopez-Rodriguez, A.B. +2 more·2019·Physiology & Behavior
DOI 10.1016/j.physbeh.2018.11.037
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Abstract

It is well known that inflammatory challenge during the prenatal period results in permanent changes in glial cells and behavior in adulthood. However, it is unknown whether inflammatory challenge during the infantile period may have permanent sexually-dimorphic effects on microglia and astrocytes in vivo, which in turn may be associated with sex differences in adult behavior. In this study, we have evaluated whether postnatal injection of lipopolysaccharide (LPS; 250μg/kg, i.p. on postnatal day 14) induces depressive and less anxiety-like behaviors, glial cell activation, pro-inflammatory cytokine (TNF-alpha) secretion and sexually dimorphic responses in adulthood. Postnatal day 14 (P14) male and female Wistar rats received an intraperitoneal (ip) injection of LPS or PBS. Three months later, animals were tested in the Open Field (OF), the Elevated Plus Maze (EPM) and the Forced Swimming Test (FST) to assess the level of anxiety and depression-like behavior. Hippocampal proinflammatory cytokine TNF-alpha concentration and the number of astrocytes and microglia were estimated in the dentate gyrus, CA1, and CA3 in two regions of the hippocampus (ventral and dorsal). Our results showed that the administration of LPS resulted in less anxiety and depression-like behavior in males but not in females. However, the LPS-administration increased the number of microglia in the dorsal and ventral hippocampus areas in females more than male, while no significant differences in TNFα level had been detected between the LPS-rats treated and their controls. Interestingly, LPS resulted in an increase in the number of astrocytes in both areas of the hippocampus in a female. While in a male, our results showed a decrease in astrocytes number in the dorsal hippocampus, but no significant differences observed in ventral hippocampus. These findings indicate that an immune challenge in infantile rats induces a ventral and dorsal hippocampus damage in female more than in male, without affecting significantly the affective behavior changes in the female. The results also showed that small changes in the male hippocampus can affect the behavior and induce a depression-like behavior.

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Authors
Berkiks, I., Garcia-Segura, L. M., Nassiri, A., Mesfioui, A., Ouichou, A., Boulbaroud, S., Bahbiti, Y., Lopez-Rodriguez, A. B., Hasnaoui, E., & El Hessni, A.
Affiliations
  • Université Ibn-Tofail (MA)
  • Université Sultan Moulay Slimane (MA)
Corresponding author
Berkiks, I.
ORCID
Venue
Physiology & Behavior
Publisher
Elsevier BV
Published
2019-02
Volume
199
Pages
386-394
ISSN
0031-9384 (ISSN-L)
DOI
10.1016/j.physbeh.2018.11.037
OpenAlex
W2905317594
Cited by
30
References
5
Citations by year
2026: 3 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 8 · 2021: 4 · 2020: 2 · 2019: 5
FWCI
1.24
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Physiology & Behavior (publishedVersion)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
Funders
  • International Brain Research Organization
  • ARC BURSARIES
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
sex differences, lipopolysaccharide, microglia, astrocytes, hippocampus, anxiety-like behavior, depression-like behavior, TNF-α, inflammatory cytokines, glial activation, prenatal inflammation, ventral hippocampus, dorsal hippocampus
MeSH terms
Animals, Anxiety, Astrocytes, Behavior, Animal, Cell Count, Depression, Female, Hippocampus, Lipopolysaccharides, Male, Pregnancy, Sex Characteristics, Tumor Necrosis Factor-alpha, Rats, Wistar, Microglia, Rats

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