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Journal Articles Science Year : 2022

Treating early postnatal circuit defect delays Huntington’s disease onset and pathology in mice

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Abstract

Recent evidence has shown that even mild mutations in the Huntingtin gene that are associated with late-onset Huntington’s disease (HD) disrupt various aspects of human neurodevelopment. To determine whether these seemingly subtle early defects affect adult neural function, we investigated neural circuit physiology in newborn HD mice. During the first postnatal week, HD mice have less cortical layer 2/3 excitatory synaptic activity than wild-type mice, express fewer glutamatergic receptors, and show sensorimotor deficits. The circuit self-normalizes in the second postnatal week but the mice nonetheless develop HD. Pharmacologically enhancing glutamatergic transmission during the neonatal period, however, rescues these deficits and preserves sensorimotor function, cognition, and spine and synapse density as well as brain region volume in HD adult mice.
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inserm-03826027 , version 1 (23-10-2022)

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Barbara Yael Braz, Doris Wennagel, Leslie Ratié, Diego Alves Rodrigues de Souza, Jean Christophe Deloulme, et al.. Treating early postnatal circuit defect delays Huntington’s disease onset and pathology in mice. Science, 2022, 377 (6613), pp.eabq5011. ⟨10.1126/science.abq5011⟩. ⟨inserm-03826027⟩
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