Distraction of olfactory bulb-medial prefrontal cortex circuit may induce anxiety-like behavior in allergic rhinitis.

Morteza Salimi,Javad Mirnajafi-Zadeh,Tannaz Parsazadegan,Milad Nazari,Meysam Zare,Sepideh Ghazvineh,Hamidreza Jamaati,Mohammad Reza Raoufy,Kolsum Dehdar,Alexandra Kavushansky

doi:10.1371/journal.pone.0221978

Abstract

Allergic rhinitis is a chronic inflammatory disease of the upper respiratory tract, which is associated with high incidence of anxiety symptom. There is evidence that medial prefrontal cortex modulates anxiety-related behaviors and receives projections from olfactory bulb. Since olfactory dysfunction has been reported in allergic rhinitis, we aimed to evaluate anxiety-like behavior and oscillations of olfactory bulb-medial prefrontal cortex circuit in an animal model of allergic rhinitis. The number of open arm entries in elevated zero maze was significantly reduced in sensitized rats exposed to intranasal ovalbumin compared to the control group, which was indicating the enhancement of anxiety-like behavior in allergic rhinitis animals. Analysis of local field potentials in olfactory bulb and medial prefrontal cortex during immobility and exploration state showed that anxiety-like behavior induced by allergic rhinitis was in association with increased activity of medial prefrontal cortex and enhancement of olfactory bulb-medial prefrontal cortex coupling in delta and theta bands. Moreover, in allergic rhinitis animals, theta strongly coordinates local gamma activity in olfactory bulb and medial prefrontal cortex, which means to have a strong local theta/gamma coupling. We suggested that disruption of olfactory bulb-medial prefrontal cortex circuit due to allergic reactions might have a governing role for inducing anxiety-like behavior in the allergic rhinitis experimental model.

Highlights

Allergic rhinitis (AR) is a chronic inflammatory disorder of the nasal mucosa, which is characterized by the presence of one or some symptoms, including itchiness, sneezing, rhinorrhea, nasal congestion, and daily alterations in sense of olfaction [1,2,3,4]
Olfactory bulb-medial prefrontal cortex circuit and anxiety-like behavior in allergic rhinitis chronic disease that affects 400 million people worldwide; and epidemiological studies have reported that 20–30% of adults and 40% of children suffer from AR [5,6,7]
The number of nose rubbing motions was assessed in order to confirm the induction of AR model in sensitized rats exposed to OVA

Summary

Introduction

Allergic rhinitis (AR) is a chronic inflammatory disorder of the nasal mucosa, which is characterized by the presence of one or some symptoms, including itchiness, sneezing, rhinorrhea, nasal congestion, and daily alterations in sense of olfaction [1,2,3,4]. It has been proposed that antigen exposure raised the level of inflammatory mediators such as interleukin-1β, which stimulated the hypothalamic-pituitaryadrenal axis and cortisol activation [16]. These reactions are known to disrupt serotonin release and led to mood changes, and induced the anxiety [17]. AR model in rodents was associated with impairment of olfactory function, increased size and number of olfactory glands, and infiltration of inflammatory cells in the olfactory mucosa [18,19] These alterations reduced local field potential (LFP) power of OB in the mouse model of AR [19]. In a human study, increased brain activity determined by magnetic resonance in the prefrontal cortex has been reported during the late phase of asthma episode [21]

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