A Sex-Specific Role of Type VII Adenylyl Cyclase in Depression

• Published in: The Journal of neuroscience Vol. 26; no. 48; pp. 12609 - 12619
• Main Authors: Hines, Lisa M, Hoffman, Paula L, Bhave, Sanjiv, Saba, Laura, Kaiser, Alan, Snell, Larry, Goncharov, Igor, LeGault, Lucie, Dongier, Maurice, Grant, Bridget, Pronko, Sergey, Martinez, Larry, Yoshimura, Masami, Tabakoff, Boris, World Health Organization/International Society for Biomedical Research on Alcoholism Study on State and Trait Markers of Alcohol Use and Dependence Investigators
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 29-11-2006; Society for Neuroscience
• Subjects: Adenylyl Cyclases - biosynthesis; Adenylyl Cyclases - genetics; Adult; Amino Acid Sequence; Animals; Depressive Disorder, Major - enzymology; Depressive Disorder, Major - genetics; Female; Genetic Linkage - genetics; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Middle Aged; Molecular Sequence Data; Polymorphism, Single Nucleotide - genetics; Sex Characteristics
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.1040-06.2006

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.