Intranasal Immune Challenge Induces Sex-Dependent Depressive-Like Behavior and Cytokine Expression in the Brain

Abstract

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-1b, tumor necrosis factor-a, and interleukin-6 in several brain regions. Increased tumor necrosis factor-a 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.

Changes in Severity of Allergy and Anxiety Symptoms Are Positively Correlated in Patients with Recurrent Mood Disorders Who Are Exposed to Seasonal Peaks of Aeroallergens

“…In any case, our results, which are consistent with our animal data (35,52), indicate that anxiety symptoms are correlated with upper respiratory inflammatory symptoms.…”

“…These data suggest that the relationship between allergic disease and depression is a major phenomenon, and seemingly more robust than the one between allergic disease and measures of anxiety. However, our animal model data point towards a more consistent association between anxiety-like behaviors rather than depressive-like behaviors and with sensitization and exposure to tree pollen allergen (35,52). To further analyze this triangular relationship between allergy, depression, and anxiety, we will continue our research with primary anxiety disorders and primary non-comorbid mood disorders.…”

Elevated cytokine expression in the orbitofrontal cortex of victims of suicide

“…In this regard, it should be highlighted that while there is abundant information about gender differences in suicide risk factors and suicidal behavior, to our knowledge, postmortem studies have not reported major neurochemical or gene expression differences between the brain of suicides women and men. The observed sex-differences in cytokine expression in the present study may be of relevance because sex-differences in the immune and cytokine response of the brain have been reported in experimental animal models (46)(47)(48). Therefore, cytokines may further our understanding of neurochemical sex-differences in the brain that may be related to sex-differences in behavior.…”

Sex differences in animal models of psychiatric disorders

“…This problem could be addressed by the use of standard and validated FST procedures already described for male rodents (Slattery and Cryan, 2012). Regarding the oestrous cycle, most studies show that the phase of the oestrous cycle does not influence basal female FST behavioural performance in a significant way (Alonso et al, 1991;Bravo and Maswood, 2006;Jans et al, 2007;Tonelli et al, 2008; Andrade et al, 2010;Craft et al, 2010; Allen et al, 2012;Kokras et al, 2012;Flores-Serrano et al, 2013). However, the oestrous cycle could play a role in antidepressant response, but the studies using standard antidepressants in intact female rats during different phases of the cycle are limited (Marvan et al, 1996;Barros and Ferigolo, 1998;Contreras et al, 1998;Consoli et al, 2005; Allen et al, 2012;Dalla et al, 2012;Flores-Serrano et al, 2013).…”