Genetically driven variation in serotonin uptake: is there a link to affective spectrum, neurodevelopmental, and neurodegenerative disorders?
Serotonin (5-HT) is an important regulator of morphogenetic activities during early central nervous system development, including cell proliferation, migration, and differentiation. The 5-HT transporter (5-HTT) plays a pivotal role in brain 5-HT homeostasis. It is also the initial target for both antidepressant drugs and drugs of abuse, some of which are potent neurotoxins. A polymorphism in the 5'-flanking regulatory region of the 5-HTT gene that results in allelic variation of 5-HTT expression is associated with anxiety-related personality traits and may influence the risk of developing affective disorders. Progress in 5-HTT gene inactivation studies are also changing views of the relevance of adaptive 5-HT uptake function in brain development and plasticity as well as processes underlying drug dependence and neurodegeneration. Despite evidence for a potential role of the 5-HTT in the integration of synaptic connections in the mammalian brain during development, adult life, and old age, detailed knowledge of the molecular mechanisms involved in these fine-tuning processes is just beginning to emerge. Integration of various strategies, including molecular genetic, transgenic, and gene transfer techniques, will allow elucidation of the 5-HTT's role in brain development, plasticity, and degeneration as well as in affective illness, drug abuse, and dementia.
Department of Psychiatry, University of Würzburg, Germany.
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Lesch
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Mössner
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000235:genetics; D000818:Animals; D001921:Brain / Q000196:embryology / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics*; D003704:Dementia / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D019964:Mood Disorders / Q000235:genetics*; D009410:Nerve Degeneration / Q000196:embryology / Q000235:genetics*; D009419:Nerve Tissue Proteins; D009473:Neuronal Plasticity / Q000235:genetics; D010551:Personality / Q000235:genetics; D011247:Pregnancy; D012307:Risk Factors; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin