Intranasal immune challenge induces sex-dependent depressive-like behavior and cytokine expression in the brain.
The association between activation of the immune system and mood disorders has been reported by several studies. However, the mechanisms by which the immune system affects mood are only partially understood. In the present study, we detected depressive-like behavior in a rat animal model which involves the induction of inflammation in the nasal cavities by intranasal (i.n.) instillation of bacterial lipopolysaccharides (LPS). Female rats showed depressive-like behavior as evidenced by the forced swim test after repeated i.n. administration of LPS. These responses were not paralleled by alterations in motor activity as measured by the open field test. In the same animals, corticosterone responses after the swimming sessions were the highest of all the groups evaluated. Real-time RT PCR was used to analyze the transcriptional regulation of the cytokines interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6 in several brain regions. Increased tumor necrosis factor-alpha was detected in the hippocampus and brainstem of female rats challenged with i.n. LPS. These results suggest that peripheral inflammation in the upper respiratory tract is an immune challenge capable of inducing depressive-like behavior, promoting exaggerated glucocorticoid responses to stress, and increasing cytokine transcription in the brain. These results further our understanding of the role that the immune system may play in the pathophysiology of depression.
Tonelli
Leonardo H
LH
Laboratory of Behavioral Neuroimmunology, Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore 21201-1549, MD, USA. Ltonelli@psych.umaryland.edu
Holmes
Andrew
A
Postolache
Teodor T
TT
D000281:Administration, Intranasal; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003863:Depression / Q000139:chemically induced* / Q000473:pathology; D030762:Estrous Cycle / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D007274:Injections, Intraperitoneal / Q000379:methods; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics; D013550:Swimming
D016207:Cytokines; D008070:Lipopolysaccharides; D003345:Corticosterone