A sex-specific role of type VII adenylyl cyclase in depression.
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.
Hines
Lisa M
LM
Department of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
Hoffman
Paula L
PL
Bhave
Sanjiv
S
Saba
Laura
L
Kaiser
Alan
A
Snell
Larry
L
Goncharov
Igor
I
LeGault
Lucie
L
Dongier
Maurice
M
Grant
Bridget
B
Pronko
Sergey
S
Martinez
Larry
L
Yoshimura
Masami
M
Tabakoff
Boris
B
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
D000262:Adenylyl Cyclases; C473265:adenylyl cyclase 7