ArticleEBioMedicine2025
Imaging brain development in a KCNQ2-developmental and epileptic encephalopathy mouse model: identifying early biomarkers for functional and structural brain changes.
Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundKCNQ2-developmental and epileptic encephalopathy (KCNQ2-DEE) is a severe neurodevelopmental disorder (NDD) characterised by early-life seizures but persistent cognitive impairment. The absence of early, quantifiable preclinical biomarkers for neurodevelopmental dysfunction limits the evaluation of new treatments. We hypothesise that key brain maturation processes are altered early in disease development and could serve as biomarkers for neurodevelopmental dysfunction.
methodsWe performed longitudinal in-vivo brain imaging in 37 kcnq2
findingsAt infant age, KI mice showed increased FC relative to WT, particularly within the default mode-like network (DMLN). During the juvenile stage, KI mice exhibited modest elevated synaptic density across brain regions, most notably in the cerebellum. By adulthood, KI mice displayed reduced FC, especially within the DMLN, compared to WT. No significant microstructural genotype-by-age interactions were found.
interpretationKCNQ2-DEE disrupts neurodevelopment, with early hyperconnectivity and delayed synaptic pruning transitioning to adult hypoconnectivity. While this pattern is too subtle to use as a standalone biomarker, these findings establish a foundation for their use in longitudinal preclinical research targeting early therapeutic intervention.
fundingSupported by the University of Antwerp, Fonds Wetenschappelijk Onderzoek, the Queen Elisabeth Medical Foundation, the European Joint Programme on Rare Disease, and Fondation Lejeune.
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