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Altered serotonin, dopamine and norepinepherine levels in 15q duplication and Angelman syndrome mouse models.

Childhood neurodevelopmental disorders like Angelman syndrome and autism may be the result of underlying defects in neuronal plasticity and ongoing problems with synaptic signaling. Some of these defects may be due to abnormal monoamine levels in different regions of the brain. Ube3a, a gene that causes Angelman syndrome (AS) when maternally deleted and is associated with autism when maternally duplicated has recently been shown to regulate monoamine synthesis in the Drosophila brain. Therefore, we examined monoamine levels in striatum, ventral midbrain, frontal cerebral cortex, cerebellar cortex and hippocampus in Ube3a deficient and Ube3a duplication animals. We found that serotonin (5HT), a monoamine affected in autism, was elevated in the striatum and cortex of AS mice. Dopamine levels were almost uniformly elevated compared to control littermates in the striatum, midbrain and frontal cortex regardless of genotype in Ube3a deficient and Ube3a duplication animals. In the duplication 15q autism mouse model, paternal but not maternal duplication animals showed a decrease in 5HT levels when compared to their wild type littermates, in accordance with previously published data. However, maternal duplication animals show no significant changes in 5HT levels throughout the brain. These abnormal monoamine levels could be responsible for many of the behavioral abnormalities observed in both AS and autism, but further investigation is required to determine if any of these changes are purely dependent on Ube3a levels in the brain.

Pubmed ID: 22916201

Authors

  • Farook MF
  • DeCuypere M
  • Hyland K
  • Takumi T
  • LeDoux MS
  • Reiter LT

Journal

PloS one

Publication Data

August 23, 2012

Associated Grants

  • Agency: NINDS NIH HHS, Id: R01NS059902

Mesh Terms

  • Angelman Syndrome
  • Animals
  • Blotting, Western
  • Brain
  • Chromatography, High Pressure Liquid
  • Disease Models, Animal
  • Dopamine
  • Gene Duplication
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Norepinephrine
  • Serotonin
  • Ubiquitin-Protein Ligases