title: Serotonin abnormalities in Engrailed-2 knockout mice: New insight relevant for a model of Autism Spectrum Disorder.
abstract: Autism spectrum disorder (ASD) is a congenital neurodevelopmental behavioral disorder that appears in early childhood. Recent human genetic studies identified the homeobox transcription factor, Engrailed 2 (EN2), as a possible ASD susceptibility gene. En2 knockout mice (En2-/-) display subtle cerebellar neuropathological changes and reduced levels of tyrosine hydroxylase, noradrenaline and serotonin in the hippocampus and cerebral cortex similar to those ones which have been observed in the ASD brain. Furthermore other similarities link En2 knockout mice to ASD patients. Several lines of evidence suggest that serotonin may play an important role in the pathophysiology of the disease. In the present study we measured, by using an HPLC, the 5-HT levels in different brain areas and at different ages in En2-/- mice. In the frontal and occipital cortex, the content of 5HT was reduced in En2-/- 1 and 3 months old mice; in 6 month old mice, the difference was still present, but it was not statistically significant. The 5-HT content of cerebellar cortex was significantly reduced at 1 month old but significantly high when the KO mice reached 3 months of age. The increase was present even at 6 months of age. A similar trend was highlighted by SERT immunolabeling in En2-/- mice compared to control in the same areas and age analyzed. Our findings, in agreement with the current knowledge on the 5-HT system alterations in ASD, confirm the early neurotransmitter deficit with a late compensatory recovery in En2 KO-mice further suggesting that this experimental animal may be considered a good predictive model for the human disease.
authors.affiliation: Department of Translational Research New Technologies in Medicine and Surgery, University of Pisa, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Viaggi
authors.affiliation: Department of Translational Research New Technologies in Medicine and Surgery, University of Pisa, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Gerace
authors.affiliation: Department of Translational Research New Technologies in Medicine and Surgery, University of Pisa, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Pardini
authors.affiliation: Department of Translational Research New Technologies in Medicine and Surgery, University of Pisa, Italy.
authors.forename: Giovanni U
authors.initials: GU
authors.lastname: Corsini
authors.affiliation: Department of Translational Research New Technologies in Medicine and Surgery, University of Pisa, Italy. Electronic address: francesca.vaglini@med.unipi.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vaglini
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D000099266:Engrailed 2 Protein
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D000099266:Engrailed 2 Protein
keywords: Animal model; Autism spectrum disorder; Cerebellum; Engrailed 2; Serotonin