Genetic Models of Serotonin (5-HT) Depletion: What do They Tell Us About the Developmental Role of 5-HT?
Article first published online: 3 SEP 2010
Copyright © 2011 Wiley-Liss, Inc.
The Anatomical Record
Special Issue: Thematic Papers: New Concepts in Developing Brain Disorders—Autism
Volume 294, Issue 10, pages 1615–1623, October 2011
How to Cite
Trowbridge, S., Narboux-Nême, N. and Gaspar, P. (2011), Genetic Models of Serotonin (5-HT) Depletion: What do They Tell Us About the Developmental Role of 5-HT?. Anat Rec, 294: 1615–1623. doi: 10.1002/ar.21248
- Issue published online: 17 SEP 2011
- Article first published online: 3 SEP 2010
- Manuscript Accepted: 9 JUL 2010
- Manuscript Received: 3 FEB 2010
- Agence Nationale pour la Recherche. Grant Number: ANR605-neur-046
- European Commission. Grant Number: FP7-health-2007-A-201714
- Université Pierre et Marie Curie
- Harvard University (Henry Russell Shaw Fellowship)
- NERF (région Ile de France)
- monoamine transporters;
- transcription factors
A large number of hyposerotonergic genetic models have been generated over the past few years. Serotonin (5-HT) depletion has been obtained via targeting of genes involved in 5-HT synthesis (Tph1 and Tph2), specification and determination of the 5-HT phenotype during development (GATA3, Pet1, and Lmx1b), and 5-HT storage or clearance (Vmat2 and SERT). Here we review these various models from a developmental perspective, beginning with a description of the sources of 5-HT during development. We then summarize the neurological and behavioral alterations that have been observed in the genetic hyposerotonergic models. Although these models appear to have normal brain development and do not exhibit any gross morphological defects, problems in somatic growth and physiological functions have been observed. Abnormal adult behavior is also seen, although whether it results from depletion of 5-HT during development or functional 5-HT deficiencies in adult life remains unclear. Evidence from these hyposerotonergic models suggests that the developing brain may not need 5-HT for the establishment of general organization and structure. However, central 5-HT appears to be necessary for postnatal body growth, maturation of respiratory and vegetative control, and possibly for the development of normal adult behavior. Anat Rec, 2011. © 2011 Wiley-Liss, Inc.