How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems

被引：164

作者：

Murphy, Dennis L. ^{[1
]}

Fox, Meredith A. ^{[1
]}

Timpano, Kiara R. ^{[1
,2
]}

Moya, Pablo R. ^{[1
]}

Ren-Patterson, Renee ^{[3
]}

Andrews, Anne M. ^{[4
,5
]}

Holmes, Andrew ^{[6
]}

Lesch, Klaus-Peter ^{[7
]}

Wendland, Jens R. ^{[1
,8
]}

机构：

[1] NIMH, Clin Sci Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA

[2] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA

[3] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA

[4] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA

[5] Penn State Univ, Huck Inst Life Sci, University Pk, PA 16802 USA

[6] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA

[7] Univ Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany

[8] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA

来源：

NEUROPHARMACOLOGY | 2008年 / 55卷 / 06期

关键词：

Homeostasis; Serotonin transporter; Anxiety; Obsessive-compulsive disorder; Depression; Epistasis;

D O I：

10.1016/j.neuropharm.2008.08.034

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Discovered and crystallized over sixty years ago, serotonin's important functions in the brain and body were identified over the ensuing years by neurochemical, physiological and pharmacological investigations. This 2008 M. Rapport Memorial Serotonin Review focuses on some of the most recent discoveries involving serotonin that are based on genetic methodologies. These include examples of the consequences that result from direct serotonergic gene manipulation (gene deletion or overexpression) in mice and other species: an evaluation of some phenotypes related to functional human serotonergic gene variants, particularly in SLC6A4, the serotonin transporter gene: and finally, a consideration of the pharmacogenomics of serotonergic drugs with respect to both their therapeutic actions and side effects. The serotonin transporter (SERT) has been the most comprehensively studied of the serotonin system molecular components, and will be the primary focus of this review. We provide in-depth examples of gene-based discoveries primarily related to SLC6A4 that have clarified serotonin's many important homeostatic functions in humans, non-human primates, mice and other species. Published by Elsevier Ltd.

引用

页码：932 / 960

页数：29

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