Ontogeny of brain and blood serotonin levels in 5-HT receptor knockout mice: potential relevance to the neurobiology of autism.
The most consistent neurochemical finding in autism has been elevated group mean levels of blood platelet 5-hydroxytryptamine (5-HT, serotonin). The origin and significance of this platelet hyperserotonemia remain poorly understood. The 5-HT(1A) receptor plays important roles in the developing brain and is also expressed in the gut, the main source of platelet 5-HT. Post-natal tissue levels of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and tryptophan were examined in the brain, duodenum and blood of 5-HT(1A) receptor-knockout and wild-type mice. At 3 days after birth, the knockout mice had lower mean brain 5-HT levels and normal mean platelet 5-HT levels. Also, at 3 days after birth, the mean tryptophan levels in the brain, duodenum and blood of the knockout mice were around 30% lower than those of the wild-type mice. By 2 weeks after birth, the mean brain 5-HT levels of the knockout mice normalized, but their mean platelet 5-HT levels became 24% higher than normal. The possible causes of these dynamic shifts were explored by examining correlations between central and peripheral levels of 5-HT, 5-HIAA and tryptophan. The results are discussed in relation to the possible role of 5-HT in the ontogeny of autism.
Janusonis
Skirmantas
S
Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut, USA. janusonis@psych.ucsb.edu
Anderson
George M
GM
Shifrovich
Ilya
I
Rakic
Pasko
P
D000818:Animals; D001321:Autistic Disorder / Q000503:physiopathology*; D001792:Blood Platelets / Q000378:metabolism; D001921:Brain / Q000254:growth & development* / Q000503:physiopathology*; D001923:Brain Chemistry / Q000502:physiology*; D002490:Central Nervous System / Q000254:growth & development; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005838:Genotype; D006897:Hydroxyindoleacetic Acid / Q000097:blood / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017933:Peripheral Nervous System / Q000254:growth & development; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D014364:Tryptophan / Q000097:blood / Q000378:metabolism
D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan