Systemic immune activation leads to neuroinflammation and sickness behavior in mice.
Substantial evidence indicates an association between clinical depression and altered immune function. Systemic administration of bacterial lipopolysaccharide (LPS) is commonly used to study inflammation-associated behavioral changes in rodents. In these experiments, we tested the hypothesis that peripheral immune activation leads to neuroinflammation and depressive-like behavior in mice. We report that systemic administration of LPS induced astrocyte activation in transgenic GFAP-luc mice and increased immunoreactivity against the microglial marker ionized calcium-binding adapter molecule 1 in the dentate gyrus of wild-type mice. Furthermore, LPS treatment caused a strong but transient increase in cytokine levels in the serum and brain. In addition to studying LPS-induced neuroinflammation, we tested whether sickness could be separated from depressive-like behavior by evaluating LPS-treated mice in a panel of behavioral paradigms. Our behavioral data indicate that systemic LPS administration caused sickness and mild depressive-like behavior. However, due to the overlapping time course and mild effects on depression-related behavior per se, it was not possible to separate sickness from depressive-like behavior in the present rodent model.
BIOMED, Hasselt University, Agoralaan C Building, 3590 Diepenbeek, Belgium ; Neuroscience, Janssen Research & Development, A Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium.
Steven
S
Biesmans
Theo F
TF
Meert
Jan A
JA
Bouwknecht
Paul D
PD
Acton
Nima
N
Davoodi
Patrick
P
De Haes
Jacobine
J
Kuijlaars
Xavier
X
Langlois
Liam J R
LJ
Matthews
Luc
L
Ver Donck
Niels
N
Hellings
Rony
R
Nuydens
D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D001522:Behavior, Animal; D001921:Brain / Q000276:immunology / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002755:Choice Behavior; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003863:Depression / Q000276:immunology*; D004195:Disease Models, Animal; D005247:Feeding Behavior; D055809:Illness Behavior; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D008070:Lipopolysaccharides / Q000737:chemistry; D049449:Luminescence; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D013395:Sucrose / Q000737:chemistry
C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D016207:Cytokines; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; D013395:Sucrose