Allergen Induces Depression-like Behavior in Association with Altered Prefrontal-hippocampal Circuit in Male Rats

Abstract

Allergic asthma is a common chronic inflammatory condition associated with psychiatric comorbidities. Notably depression, correlated with adverse outcomes in asthmatic patients. Peripheral inflammation's role in depression has been shown previously. However, evidence regarding the effects of allergic asthma on the medial prefrontal cortex (mPFC)-ventral hippocampus (vHipp) interactions, an important neurocircuitry in affective regulation, is yet to be demonstrated. Herein, we investigated the effects of allergen exposure in sensitized rats on the immunoreactivity of glial cells, depression-like behavior, brain regions volume, as well as activity and connectivity of the mPFC-vHipp circuit. We found that allergen-induced depressive-like behavior was associated with more activated microglia and astrocytes in mPFC and vHipp, as well as reduced hippocampus volume. Intriguingly, depressive-like behavior was negatively correlated with mPFC and hippocampus volumes in the allergen-exposed group. Moreover, mPFC and vHipp activity were altered in asthmatic animals. Allergen disrupted the strength and direction of functional connectivity in the mPFC-vHipp circuit so that, unlike normal conditions, mPFC causes and modulates vHipp activity. Our results provide new insight into the underlying mechanism of allergic inflammation-induced psychiatric disorders, aiming to develop new interventions and therapeutic approaches for improving asthma complications.