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Calcium-Sensitive Adenylyl Cyclases in Depression and Anxiety: Behavioral and Biochemical Consequences of Isoform Targeting

Title
Calcium-Sensitive Adenylyl Cyclases in Depression and Anxiety: Behavioral and Biochemical Consequences of Isoform Targeting
Authors
Krishnan V.Graham A.Mazei-Robison M.S.Lagace D.C.Kim K.-S.Birnbaum S.Eisch A.J.Han P.-L.Storm D.R.Zachariou V.Nestler E.J.
Ewha Authors
한평림
SCOPUS Author ID
한평림scopus
Issue Date
2008
Journal Title
Biological Psychiatry
ISSN
0006-3223JCR Link
Citation
vol. 64, no. 4, pp. 336 - 343
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Background: Adenylyl cyclases (ACs) represent a diverse family of enzymes responsible for the generation of cyclic adenosine monophosphate (cAMP), a key intracellular second messenger. The Ca2+/calmodulin-stimulated AC1 and AC8 isoforms as well as the calcium-inhibited AC5 isoform are abundantly expressed within limbic regions of the central nervous system. This study examines the contribution of these AC isoforms to emotional behavior. Methods: Male and female AC1/8 double knockout mice (DKO) and AC5 knockout mice (AC5KO) were examined on a series of standard laboratory assays of emotionality. Mice were also assayed for hippocampal cell proliferation and for changes in brain-derived neurotrophic factor signaling in the nucleus accumbens, amygdala, and hippocampus, three forebrain structures involved in the regulation of mood and affect. Results: The AC5KO mice showed striking anxiolytic and antidepressant phenotypes on standard behavioral assays. In contrast, AC1/8 DKO mice were hypoactive, exhibited diminished sucrose preference, and displayed alterations in neurotrophic signaling, generally consistent with a prodepressant phenotype. Neither line of mice displayed alterations in hippocampal cell proliferation. Conclusions: These data illustrate the complex manner in which Ca2+/calmodulin-stimulated ACs contribute to emotional behavior. In addition, they support the possibility that a selective AC5 antagonist would be of therapeutic value against depression and anxiety disorders. © 2008 Society of Biological Psychiatry.
DOI
10.1016/j.biopsych.2008.03.026
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일반대학원 > 뇌·인지과학과 > Journal papers
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