Dystrophic Serotonin Axons in Postmortem Brains from Young Autism Patients
Article first published online: 8 SEP 2011
Copyright © 2011 Wiley-Liss, Inc.
The Anatomical Record
Special Issue: Thematic Papers: New Concepts in Developing Brain Disorders—Autism
Volume 294, Issue 10, pages 1653–1662, October 2011
How to Cite
Azmitia, E. C., Singh, J. S., Hou, X. P. and Wegiel, J. (2011), Dystrophic Serotonin Axons in Postmortem Brains from Young Autism Patients. Anat Rec, 294: 1653–1662. doi: 10.1002/ar.21243
- Issue published online: 17 SEP 2011
- Article first published online: 8 SEP 2011
- Manuscript Accepted: 1 JUL 2010
- Manuscript Received: 12 MAR 2010
- NYU Challenge Grant
Autism causes neuropathological changes in varied anatomical loci. A coherent neural mechanism to explain the spectrum of autistic symptomatology has not been proposed because most anatomical researchers focus on point-to-point functional neural systems (e.g., auditory and social networks) rather than considering global chemical neural systems. Serotonergic neurons have a global innervation pattern. Disorders Research Program, AS073234, Program Project (JW). Their cell bodies are found in the midbrain but they project their axons throughout the neural axis beginning in the fetal brain. This global system is implicated in autism by animal models and by biochemical, imaging, pharmacological, and genetics studies. However, no anatomical studies of the 5-HT innervation of autistic donors have been reported. Our review presents immunocytochemical evidence of an increase in 5-HT axons in postmortem brain tissue from autism donors aged 2.8–29 years relative to controls. This increase is observed in the principle ascending fiber bundles of the medial and lateral forebrain bundles, and in the innervation density of the amygdala and the piriform, superior temporal, and parahippocampal cortices. In autistic donors 8 years of age and up, several types of dystrophic 5-HT axons were seen in the termination fields. One class of these dystrophic axons, the thick heavily stained axons, was not seen in the brains of patients with neurodegenerative diseases. These findings provide morphological evidence for the involvement of serotonin neurons in the early etiology of autism, and suggest new therapies may be effective to blunt serotonin's trophic actions during early brain development in children. Anat Rec, 2011. © 2011 Wiley-Liss, Inc.