title: Chronic anosmia induces depressive behavior and reduced anxiety via dysregulation of glucocorticoid receptor and corticotropin-releasing hormone in a mouse model.
abstract: Olfactory loss is highly prevalent, and comorbid mood disorders are common. Considering olfactory input is highly interconnected with the limbic system, and that the limbic system manages mood, it is predictable that impairments in the sense of smell may result in mood changes.
  
  
  
  Chronic olfactory deficits were induced by repeated intranasal irrigation of ZnSO4 for 12 weeks 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.
  
  
  
  Disruption of the olfactory epithelium and olfactory loss was confirmed in histological studies and potato chip finding test. Behavioral tests show that the chronic anosmic state caused increased depression and reduced anxiety. PCR data showed that mRNA levels of GR in the hypothalamus and CRH in the amygdala were significantly decreased.
  
  
  
  These results propose that ZnSO4-induced chronic anosmia can cause a depressive and anxiolytic state via decreased hypothalamic GR and amygdalar CRH.
authors.affiliation: Department of Pharmacology and Biological Sciences, Seoul National University College of Medicine, Republic of Korea.
authors.forename: Sangzin
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Department of Pharmacology and Biological Sciences, Seoul National University College of Medicine, Republic of Korea.
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Shin
authors.affiliation: Seoul National University College of Natural Sciences, Republic of Korea.
authors.forename: Usman
authors.initials: U
authors.lastname: Mahmood
authors.affiliation: Department of Pharmacology and Biological Sciences, Seoul National University College of Medicine, Republic of Korea.
authors.forename: Roza
authors.initials: R
authors.lastname: Khalmuratova
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Gyeongsang National University College of Medicine, Jinju, Republic of Korea.
authors.forename: Sea-Yuong
authors.initials: SY
authors.lastname: Jeon
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hong Ryul
authors.initials: HR
authors.lastname: Jin
authors.affiliation: Department of Psychiatry, Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung-Seok
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Pharmacology and Biological Sciences, Seoul National University College of Medicine, Republic of Korea.
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dae Woo
authors.initials: DW
authors.lastname: Kim
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D003863:Depression / Q000209:etiology* / Q000378:metabolism; D004195:Disease Models, Animal; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D008807:Mice, Inbred BALB C; D000857:Olfaction Disorders / Q000378:metabolism / Q000473:pathology / Q000523:psychology*; D009831:Olfactory Mucosa / Q000473:pathology; D011897:Random Allocation; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D019287:Zinc Sulfate
chemical_list: D011965:Receptors, Glucocorticoid; D019287:Zinc Sulfate; D003346:Corticotropin-Releasing Hormone