ZnSO4에 의한 후각상실 마우스 모델에서의 기분장애에 대한 연구

Abstract

Introduction: Olfactory loss is highly prevalent and is commonly accompanied by comorbid mood disorders. Considering olfactory input is highly interconnected with the limbic system and the limbic system is the brain region that manages mood, it is predictable that impairments in the sense of smell may result in mood changes. However, olfaction is the most neglected among the five senses in clinics as well as research, resulting in sparse reports regarding the impacts of olfactory deficits on the brain.

Methods: Chronic anosmia was induced by repeated intranasal irrigation of ZnSO4 for 12 weeks, while acute anosmia was induced by a single treatment of ZnSO4 in BALB/c mice. H&E staining, OMP staining, and potato chip finding test were performed to confirm olfactory loss. Tail suspension, forced swim, and splash tests were performed to evaluate depression, as well as open field, elevated plus maze tests were applied to assess anxiety. The mRNA levels of glucocorticoid receptor (GR) and corticotropin releasing hormone (CRH) were measured by real-time PCR to confirm relevant molecular changes.

Results: Disruption of the olfactory epithelium and olfactory loss was confirmed by histological analyses and potato chip finding test. Behavioral tests showed that both chronic and acute anosmia resulted in increased depression and reduced anxiety. PCR data showed that mRNA levels of GR in the hypothalamus were reduced in the chronic model and that CRH expression in the amygdala was decreased in both the chronic and acute model.

Conclusions: These results propose that ZnSO4-induced acquired anosmia can cause a depressive and anxiolytic state via decreased hypothalamic GR and/or amygdalar CRH.