title: Subregion-specific decreases in hippocampal serotonin transporter protein expression and function associated with endophenotypes of depression.
abstract: Stress influences the development of depression, and depression is associated with structural and functional changes in the hippocampus. The current study sought to determine whether chronic corticosteroid (CORT) treatment influences serotonin transporter (5-HTT) protein expression and function in the CA1, CA3, and dentate gyrus (DG) subregions of the hippocampus. Male CD-1 mice were subcutaneously injected with CORT at a dose of 20 mg/kg once daily for 3 weeks. Behavioral state was assessed using sucrose preference, physical state of the coat, forced swimming test, and tail suspension test. We then determine 5-HTT protein expression and synaptosomal 5-HT uptake in the CA1, CA3 and DG subregions. CORT treatment induced anhedonia and behavioral despair, two core endophenotypes of clinical depression; 5-HTT protein expression levels and synaptosomal 5-HT uptake were both decreased in a subregion-specific manner, with the greatest decrease observed in the DG, a moderate decrease in the CA3, and the CA1 showed no apparent change. In addition, a reduction in tissue mass was detected in the DG following the CORT treatment. These data indicate that subregion-specific decreases in hippocampal 5-HTT protein expression and function are associated with endophenotypes of depression.
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.
authors.forename: Man
authors.initials: M
authors.lastname: Tang
authors.forename: Tao
authors.initials: T
authors.lastname: He
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.forename: Qing-Yan
authors.initials: QY
authors.lastname: Meng
authors.forename: Yao
authors.initials: Y
authors.lastname: Diao
authors.forename: Jie-Yu
authors.initials: JY
authors.lastname: Lei
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: He
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Xiu-Bo
authors.initials: XB
authors.lastname: Sang
authors.forename: Shulei
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000305:Adrenal Cortex Hormones; D059445:Anhedonia / Q000502:physiology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D056654:CA3 Region, Hippocampal / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology; D003866:Depressive Disorder / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D058068:Endophenotypes; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size; D011897:Random Allocation; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D000305:Adrenal Cortex Hormones; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D012701:Serotonin
keywords: anhedonia; behavioral despair; corticosteroid; hippocampus; synaptosomal 5-HT uptake