Connections between autism, serotonin and hedgehog signaling

  • Awarded: 2011
  • Award Type: Research
  • Award #: 202084

The chemical messenger serotonin has long been associated with autism. Serotonin is made in the blood and in the brain. In the brain, it is made by a specialized group of neurons in the brainstem and functions as a neurotransmitter, influencing the activity of neurons in virtually all regions. How abnormal serotonin function contributes to some of the key behaviors that define autism is not clear, but serotonin has been shown to affect the development and function of synapses, the junctions between brain cells. This is consistent with the idea that autism might be a disorder of the synapse.

The genetic disease Smith-Lemli-Opitz syndrome (SLOS) is strongly associated with autism. A genetic mouse model of this disease displays strikingly abnormal development of brain cells that use serotonin as a neurotransmitter. The generation of these neurons depends on a signaling molecule called sonic hedgehog (SHH), the function of which is perturbed in SLOS. Interestingly, genetic mutations of certain factors that regulate SHH function are also associated with autism.

James Briscoe, John Jacob and their colleagues plan to investigate whether abnormal SHH function impairs the generation of brain cells that produce serotonin. By analyzing the molecular makeup of these neurons in the mouse model of SLOS and by taking advantage of powerful techniques, including mass spectrometry, the researchers hope to identify the molecular defect in SLOS that is responsible for abnormal development of serotonin-producing brain cells. This would be a critical step on the road to understanding the underlying causes of autism, and could help to identify new drugs to treat the disorder’s key symptoms.

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