Ontogeny of brain and blood serotonin levels in 5-HT receptor knockout mice: potential relevance to the neurobiology of autism

J Neurochem. 2006 Nov;99(3):1019-31. doi: 10.1111/j.1471-4159.2006.04150.x. Epub 2006 Sep 18.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autistic Disorder / physiopathology*
  • Blood Platelets / metabolism
  • Brain / growth & development*
  • Brain / physiopathology*
  • Brain Chemistry / physiology*
  • Central Nervous System / growth & development
  • Chromatography, High Pressure Liquid
  • Female
  • Genotype
  • Hydroxyindoleacetic Acid / blood
  • Hydroxyindoleacetic Acid / metabolism
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peripheral Nervous System / growth & development
  • Receptor, Serotonin, 5-HT1A / genetics
  • Receptor, Serotonin, 5-HT1A / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serotonin / blood
  • Serotonin / metabolism*
  • Tryptophan / blood
  • Tryptophan / metabolism

Substances

  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Tryptophan