Affiliation:
1. Ottawa Hospital Research Institute (Neuroscience), University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5
Abstract
The serotonin-1A (5-HT
1A
) receptor is an abundant post-synaptic 5-HT receptor (heteroreceptor) implicated in regulation of mood, emotion and stress responses and is the major somatodendritic autoreceptor that negatively regulates 5-HT neuronal activity. Based on animal models, an integrated model for opposing roles of pre- and post-synaptic 5-HT
1A
receptors in anxiety and depression phenotypes and response to antidepressants is proposed. Understanding differential transcriptional regulation of pre- versus post-synaptic 5-HT
1A
receptors could provide better tools for their selective regulation. This review examines the transcription factors that regulate brain region-specific basal and stress-induced expression of the 5-HT
1A
receptor gene (
Htr1a
). A functional polymorphism, rs6295 in the
Htr1a
promoter region, blocks the function of specific repressors Hes1, Hes5 and Deaf1, resulting in increased 5-HT
1A
autoreceptor expression in animal models and humans. Its association with altered 5-HT
1A
expression, depression, anxiety and antidepressant response are related to genotype frequency in different populations, sample homogeneity, disease outcome measures and severity. Preliminary evidence from gene × environment studies suggests the potential for synergistic interaction of stress-mediated repression of 5-HT
1A
heteroreceptors, and rs6295-induced upregulation of 5-HT
1A
autoreceptors. Targeted therapeutics to inhibit 5-HT
1A
autoreceptor expression and induce 5-HT
1A
heteroreceptor expression may ameliorate treatment of anxiety and major depression.
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology
Cited by
101 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献