title: Impaired adrenal medullary function in a mouse model of depression induced by unpredictable chronic stress.
abstract: Stress has been considered determinant in the etiology of depression. The adrenal medulla plays a key role in response to stress by releasing catecholamines, which are important to maintain homeostasis. We aimed to study the adrenal medulla in a mouse model of depression induced by 21 days of unpredictable chronic stress (UCS). We observed that UCS induced a differential and time-dependent change in adrenal medulla. After 7 days of UCS, mice did not show depressive-like behavior, but the adrenal medullae show increased protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH and PNMT), Neuropeptide Y, the SNARE protein SNAP-25, the catecholamine transporter VMAT2 and the chromaffin progenitor cell markers, Mash1 and Phox2b. Moreover, 7 days of UCS induced a decrease in the chromaffin progenitor cell markers, Sox9 and Notch1. This suggests an increased capacity of chromaffin cells to synthesize, store and release catecholamines. In agreement, after 7 days, UCS mice had higher NE and EP levels in adrenal medulla. Opposite, when mice were submitted to 21 days of UCS, and showed a depressive like behavior, adrenal medullae had lower protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH, PNMT), catecholamine transporters (NET, VMAT1), SNARE proteins (synthaxin1A, SNAP25, VAMP2), catecholamine content (EP, NE), and lower EP serum levels, indicating a reduction in catecholamine synthesis, re-uptake, storage and release. In conclusion, this study suggests that mice exposed to UCS for a period of 21 days develop a depressive-like behavior accompanied by an impairment of adrenal medullary function.
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
authors.forename: Magda M
authors.initials: MM
authors.lastname: Santana
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Rosmaninho-Salgado
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Vera
authors.initials: V
authors.lastname: Cortez
authors.affiliation: IBILI - Faculty of Medicine, University of Coimbra, Coimbra 3000-548, Portugal.
authors.forename: Frederico C
authors.initials: FC
authors.lastname: Pereira
authors.affiliation: Department of Biochemistry, Universidade Federal de Santa Catarina (UFSC), Florianópolis, Brazil.
authors.forename: Manuella P
authors.initials: MP
authors.lastname: Kaster
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Célia A
authors.initials: CA
authors.lastname: Aveleira
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Marisa
authors.initials: M
authors.lastname: Ferreira
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Álvaro
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal. Electronic address: ccavadas@uc.pt.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Cavadas
mesh_terms: D000313:Adrenal Medulla / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001835:Body Weight; D050482:Catecholamine Plasma Membrane Transport Proteins / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D002837:Chromaffin Granules / Q000502:physiology; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D003866:Depressive Disorder / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology; D013315:Stress, Psychological / Q000473:pathology / Q000503:physiopathology*; D035501:Uncertainty
chemical_list: D050482:Catecholamine Plasma Membrane Transport Proteins; D002395:Catecholamines; D012333:RNA, Messenger; D003345:Corticosterone