Pucilowska, Joanna, Vithayathil, Joseph, Pagani, Marco, Kelly, Caitlin, Karlo, J. Colleen, Robol, Camila, Morella, Ilaria ORCID: https://orcid.org/0000-0001-5691-5400, Gozzi, Alessandro, Brambilla, Riccardo ORCID: https://orcid.org/0000-0003-3569-5706 and Landreth, Gary E. 2018. Pharmacological inhibition of ERK signaling rescues pathophysiology and behavioral phenotype associated with 16p11.2 chromosomal deletion in mice. Journal of Neuroscience 38 (30) , pp. 6640-6652. 10.1523/JNEUROSCI.0515-17.2018 |
Preview |
PDF
- Accepted Post-Print Version
Download (1MB) | Preview |
Abstract
The human 16p11.2 microdeletion is one of the most common gene copy number variations linked to autism, but the pathophysiology associated with this chromosomal abnormality is largely unknown. The 593 kb deletion contains the ERK1 gene and other genes that converge onto the ERK/MAP kinase pathway. Perturbations in ERK signaling are linked to a group of related neurodevelopmental disorders hallmarked by intellectual disability, including autism. We report that mice harboring the 16p11.2 deletion exhibit a paradoxical elevation of ERK activity, cortical cytoarchitecture abnormalities and behavioral deficits. Importantly, we show that treatment with a novel ERK pathway inhibitor during a critical period of brain development rescues the molecular, anatomical and behavioral deficits in the 16p11.2 deletion mice. The ERK inhibitor treatment administered to adult mice ameliorates a subset of these behavioral deficits. Our findings provide evidence for potential targeted therapeutic intervention in 16p11.2 deletion carriers.
Item Type: | Article |
---|---|
Date Type: | Publication |
Status: | Published |
Schools: | Biosciences |
Publisher: | Society for Neuroscience |
ISSN: | 0270-6474 |
Date of First Compliant Deposit: | 7 June 2018 |
Date of Acceptance: | 6 June 2018 |
Last Modified: | 24 Nov 2024 11:15 |
URI: | https://orca.cardiff.ac.uk/id/eprint/112105 |
Citation Data
Cited 61 times in Scopus. View in Scopus. Powered By Scopus® Data
Actions (repository staff only)
Edit Item |