Functional role of Calcium-stimulated adenylyl cyclase 8 in adaptations to psychological stressors in the mouse: implications for mood disorders.
Summary of "Functional role of Calcium-stimulated adenylyl cyclase 8 in adaptations to psychological stressors in the mouse: implications for mood disorders."
The Ca(2+)/calmodulin stimulated adenylyl cylcase 8 (AC8) is a pure Ca(2+) sensor, catalyzing the conversion of ATP to cAMP, with a critical role in neuronal plasticity. A role for AC8 in modulating complex behavioral outcomes has been demonstrated in AC8 knock out (KO) mouse models in which anxiety-like responses were differentially modulated following repeated stress experiences, suggesting an involvement of AC8 in stress adaptation and mood disorders. To further investigate the role of this enzyme in phenotypes relevant for psychiatric conditions, AC8 KO mice were assessed for baseline behavioral and hormonal parameters, responses to repeated restraint stress experience, and long-term effects of chronic social defeat stress. The lack of AC8 conferred a hyperactive-phenotype both in home-cage behaviors and the forced swim test response as well as lower leptin plasma levels and adrenal hypertrophy. AC8 KO mice showed baseline "anxiety" levels similar to wild type littermates in a variety of procedures, but displayed decreased anxiety-like responses following repeated restraint stress. This increased stress resilience was not seen during the chronic social defeat procedure. AC8 KO did not differ from wild type mice in response to social stress; similar alterations in body weight, food intake and increased social avoidance were found in all defeated subjects. Altogether these results support a complex role of cAMP signaling pathways confirming the involvement of AC8 in the modulation of stress responses. Furthermore, the hyperactivity and the increased risk taking behavior observed in AC8 KO mice could be related to a manic-like behavioral phenotype that warrants further investigation.
Affiliation
Neurosciences CEDD, GlaxoSmithKline Medicine Research Centre, via Fleming 4, 37135 Verona, Italy. maria.razzoli@aptuit.com
Journal Details
This article was published in the following journal.
Name: Neuroscience
ISSN: 1873-7544
Pages: 429-40
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20638449
- DOI: http://dx.doi.org/10.1016/j.neuroscience.2010.07.022
Medical and Biotech [MESH] Definitions
Guanylate Cyclase-activating Proteins
Neuronal calcium sensor proteins that regulate the activation of membrane-bound GUANYLATE CYCLASE. They are primarily expressed in the RETINA where they play an important role in PHOTOTRANSDUCTION.
Dopamine And Camp-regulated Phosphoprotein 32
A phosphoprotein that was initially identified as a major target of DOPAMINE activated ADENYLYL CYCLASE in the CORPUS STRIATUM. It regulates the activities of PROTEIN PHOSPHATASE-1 and PROTEIN KINASE A, and it is a key mediator of the biochemical, electrophysiological, transcriptional, and behavioral effects of DOPAMINE.
Receptors, Calcium-sensing
A class of G-protein-coupled receptors that react to varying extracellular CALCIUM levels. Calcium-sensing receptors in the PARATHYROID GLANDS play an important role in the maintenance of calcium HOMEOSTASIS by regulating the release of PARATHYROID HORMONE. They differ from INTRACELLULAR CALCIUM-SENSING PROTEINS which sense intracellular calcium levels.
Parathyroid Hormone
A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates.
Plasma Membrane Calcium-transporting Atpases
Calcium-transporting ATPases found on the PLASMA MEMBRANE that catalyze the active transport of CALCIUM from the CYTOPLASM into the extracellular space. They play a role in maintaining a CALCIUM gradient across plasma membrane.
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