title: Reduced phosphorylation of synapsin I in the hippocampus of Engrailed-2 knockout mice, a model for autism spectrum disorders.
abstract: Mice lacking the homeodomain transcription factor Engrailed-2 (En2(-/-) mice) are a well-characterized model for autism spectrum disorders (ASD). En2(-/-) mice present molecular, neuropathological and behavioral deficits related to ASD, including down-regulation of ASD-associated genes, cerebellar hypoplasia, interneuron loss, enhanced seizure susceptibility, decreased sociability and impaired cognition. Specifically, impaired spatial learning in the Morris water maze (MWM) is associated with reduced expression of neurofibromin and increased phosphorylation of extracellular-regulated kinase (ERK) in the hippocampus of En2(-/-) adult mice. In the attempt to better understand the molecular cascades underlying neurofibromin-dependent cognitive deficits in En2 mutant mice, we investigated the expression and phosphorylation of synapsin I (SynI; a major target of neurofibromin-dependent signaling) in the hippocampus of wild-type (WT) and En2(-/-) mice before and after MWM. Here we show that SynI mRNA and protein levels are down-regulated in the hippocampus of naïve and MWM-treated En2(-/-) mice, as compared to WT controls. This down-regulation is paralleled by reduced levels of SynI phosphorylation at Ser549 and Ser553 residues in the hilus of mutant mice, before and after MWM. These data indicate that in En2(-/-) hippocampus, neurofibromin-dependent pathways converging on SynI phosphorylation might underlie hippocampal-dependent learning deficits observed in En2(-/-) mice.
authors.affiliation: Laboratory of Molecular Neuropathology, Centre for Integrative Biology, University of Trento, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Provenzano
authors.affiliation: Laboratory of Molecular Neuropathology, Centre for Integrative Biology, University of Trento, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pangrazzi
authors.affiliation: Laboratory of Molecular Neuropathology, Centre for Integrative Biology, University of Trento, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Poli
authors.affiliation: Laboratory of Molecular Neuropathology, Centre for Integrative Biology, University of Trento, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Sgadò
authors.affiliation: Institute of Neuroscience, CNR, Pisa, Italy; NEUROFARBA Department, University of Florence, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Berardi
authors.affiliation: Laboratory of Molecular Neuropathology, Centre for Integrative Biology, University of Trento, Italy; Institute of Neuroscience, CNR, Pisa, Italy. Electronic address: bozzi@science.unitn.it.
authors.forename: Y
authors.initials: Y
authors.lastname: Bozzi
mesh_terms: D000818:Animals; D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000378:metabolism* / Q000523:psychology; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010766:Phosphorylation; D015398:Signal Transduction; D065853:Spatial Learning / Q000502:physiology*; D016704:Synapsins / Q000378:metabolism*; D000099266:Engrailed 2 Protein
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D016704:Synapsins; D000099266:Engrailed 2 Protein
keywords: ERK; autism; learning; mouse; neurotransmission; synapse