title: A sex-specific role of type VII adenylyl cyclase in depression.
abstract: Major depression represents a complex mental disorder. The identification of biological markers that define subtypes of major depressive disorder would greatly facilitate appropriate medical treatments, as well as provide insight into etiology. Reduced activity of the cAMP signaling system has been implicated in the etiology of major depression. Previous work has shown low adenylyl cyclase activity in platelets and postmortem brain tissue of depressed individuals. Here, we investigate the role of the brain type VII isoform of adenylyl cyclase (AC7) in the manifestation of depressive symptoms in genetically modified animals, using a combination of in vivo behavioral experiments, gene expression profiling, and bioinformatics. We also completed studies with humans on the association of polymorphisms in the AC7 gene with major depressive illness (unipolar depression) based on Diagnostic and Statistical Manual of Mental Disorders IV criteria. Collectively, our results demonstrate a sex-specific influence of the AC7 gene on a heritable form of depressive illness.
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Hines
authors.forename: Paula L
authors.initials: PL
authors.lastname: Hoffman
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Bhave
authors.forename: Laura
authors.initials: L
authors.lastname: Saba
authors.forename: Alan
authors.initials: A
authors.lastname: Kaiser
authors.forename: Larry
authors.initials: L
authors.lastname: Snell
authors.forename: Igor
authors.initials: I
authors.lastname: Goncharov
authors.forename: Lucie
authors.initials: L
authors.lastname: LeGault
authors.forename: Maurice
authors.initials: M
authors.lastname: Dongier
authors.forename: Bridget
authors.initials: B
authors.lastname: Grant
authors.forename: Sergey
authors.initials: S
authors.lastname: Pronko
authors.forename: Larry
authors.initials: L
authors.lastname: Martinez
authors.forename: Masami
authors.initials: M
authors.lastname: Yoshimura
authors.forename: Boris
authors.initials: B
authors.lastname: Tabakoff
mesh_terms: D000262:Adenylyl Cyclases / Q000096:biosynthesis* / Q000235:genetics*; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D003865:Major Depressive Disorder / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012727:Sex Characteristics
chemical_list: D000262:Adenylyl Cyclases; C473265:adenylyl cyclase 7