Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6273066 | Neuroscience | 2015 | 9 Pages |
â¢Synapsin I mRNA and protein are down-regulated in the hippocampus of En2â/â mice.â¢Synapsin I phosphorylation is reduced in the En2â/â hippocampus, both before and after spatial learning.â¢Different signaling pathways downstream of neurofibromin regulate synapsin I phosphorylation in the En2â/â hippocampus.
Mice lacking the homeodomain transcription factor Engrailed-2 (En2â/â mice) are a well-characterized model for autism spectrum disorders (ASD). En2â/â 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 En2â/â 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 En2â/â 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 En2â/â 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 En2â/â hippocampus, neurofibromin-dependent pathways converging on SynI phosphorylation might underlie hippocampal-dependent learning deficits observed in En2â/â mice.