ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Hippocampal dysregulation of neurofibromin-dependent pathways is associated with impaired spatial learning in engrailed 2 knock-out mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 25 citations in OpenAlex.
- Comprehensive mapping of Neurofibromin (NF1) expression in developing mouse brain.Brain structure & function · 2026Article
- Comprehensive mapping of Neurofibromin (NF1) expression in developing mouse brain.bioRxiv : the preprint server for biology · 2026Article
- Inhibition of GSK3α,β rescues cognitive phenotypes in a preclinical mouse model of CTNNB1 syndrome.EMBO molecular medicine · 2024Article
- Influences of RASopathies on Neuroanatomical Variation in Children.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2024Article
- One-carbon metabolism is required for epigenetic stability in the mouse placenta.Frontiers in cell and developmental biology · 2023Article
- Abnormal Whisker-Dependent Behaviors and Altered Cortico-Hippocampal Connectivity in Shank3b-/- Mice.Cerebral cortex (New York, N.Y. : 1991) · 2022Article
- Review
- Article
- Aberrant Somatosensory Processing and Connectivity in Mice LackingThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia.The EMBO journal · 2017Article
- Comparative Gene Expression Analysis of Two Mouse Models of Autism: Transcriptome Profiling of the BTBR and En2 (-/-) Hippocampus.Frontiers in neuroscience · 2016Article
- Immunohistochemical visualization of hippocampal neuron activity after spatial learning in a mouse model of neurodevelopmental disorders.Journal of visualized experiments : JoVE · 2015Article
- Synapses as therapeutic targets for autism spectrum disorders: an international symposium held in pavia on july 4th, 2014.Frontiers in cellular neuroscience · 2014Review
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10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome-wide association studies indicated the homeobox-containing transcription factor Engrailed-2 (En2) as a candidate gene for autism spectrum disorders (ASD). Accordingly, En2 knock-out (En2(-/-)) mice show anatomical and behavioral "ASD-like" features, including decreased sociability and learning deficits. The molecular pathways underlying these deficits in En2(-/-) mice are not known. Deficits in signaling pathways involving neurofibromin and extracellular-regulated kinase (ERK) have been associated with impaired learning. Here we investigated the neurofibromin-ERK cascade in the hippocampus of wild-type (WT) and En2(-/-) mice before and after spatial learning testing. When compared with WT littermates, En2(-/-) mice showed impaired performance in the Morris water maze (MWM), which was accompanied by lower expression of the activity-dependent gene Arc. Quantitative RT-PCR, immunoblotting, and immunohistochemistry experiments showed a marked downregulation of neurofibromin expression in the dentate gyrus of both naive and MWM-treated En2(-/-) mice. ERK phosphorylation, known to be induced in the presence of neurofibromin deficiency, was increased in the dentate gyrus of En2(-/-) mice after MWM. Treatment of En2(-/-) mice with lovastatin, an indirect inhibitor of ERK phosphorylation, markedly reduced ERK phosphorylation in the dentate gyrus, but was unable to rescue learning deficits in MWM-trained mutant mice. Further investigation is needed to unravel the complex molecular mechanisms linking dysregulation of neurofibromin-dependent pathways to spatial learning deficits in the En2 mouse model of ASD.
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