Format

Send to

Choose Destination
See comment in PubMed Commons below
Pharmacol Ther. 2011 Jul;131(1):61-79. doi: 10.1016/j.pharmthera.2011.03.013. Epub 2011 Apr 5.

Ontogeny and regulation of the serotonin transporter: providing insights into human disorders.

Author information

1
Department of Physiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7756, San Antonio, TX 78229-3900, USA. daws@uthscsa.edu

Abstract

Serotonin (5-hydroxytryptamine, 5-HT) was one of the first neurotransmitters for which a role in development was identified. Pharmacological and gene knockout studies have revealed a critical role for 5-HT in numerous processes, including cell division, neuronal migration, differentiation and synaptogenesis. An excess in brain 5-HT appears to be mechanistically linked to abnormal brain development, which in turn is associated with neurological disorders. Ambient levels of 5-HT are controlled by a vast orchestra of proteins, including a multiplicity of pre- and post-synaptic 5-HT receptors, heteroreceptors, enzymes and transporters. The 5-HT transporter (SERT, 5-HTT) is arguably the most powerful regulator of ambient extracellular 5-HT. SERT is the high-affinity uptake mechanism for 5-HT and exerts tight control over the strength and duration of serotonergic neurotransmission. Perturbation of its expression level or function has been implicated in many diseases, prominent among them are psychiatric disorders. This review synthesizes existing information on the ontogeny of SERT during embryonic and early postnatal development though adolescence, along with factors that influence its expression and function during these critical developmental windows. We integrate this knowledge to emphasize how inappropriate SERT expression or its dysregulation may be linked to the pathophysiology of psychiatric, cardiovascular and gastrointestinal diseases.

PMID:
21447358
PMCID:
PMC3131109
DOI:
10.1016/j.pharmthera.2011.03.013
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center