Prenatal ethanol exposure impairs hippocampal plasticity and cognition in adolescent mice.

Autor: Curti L; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy., Rizzi B; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Italy, University of Florence, Florence, Italy., Mottarlini F; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Italy, University of Florence, Florence, Italy., Bigagli E; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy., Ilari A; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy., Costa A; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy., Sordi V; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy; School of Pharmacy, Pharmacology Unit, Centre for Neuroscience, University of Camerino, Via Madonna delle Carceri 9, 62032 Camerino, Italy., Ranieri G; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy., Luceri C; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy., Cannella N; School of Pharmacy, Pharmacology Unit, Centre for Neuroscience, University of Camerino, Via Madonna delle Carceri 9, 62032 Camerino, Italy., Ubaldi M; School of Pharmacy, Pharmacology Unit, Centre for Neuroscience, University of Camerino, Via Madonna delle Carceri 9, 62032 Camerino, Italy., Masi A; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy., Fumagalli F; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Italy, University of Florence, Florence, Italy., Caffino L; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Italy, University of Florence, Florence, Italy., Mannaioni G; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy., Gerace E; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy; Department of Health Sciences, University of Florence, Florence, Italy. Electronic address: elisabetta.gerace@unifi.it.
Jazyk: angličtina
Zdroj: Progress in neuro-psychopharmacology & biological psychiatry [Prog Neuropsychopharmacol Biol Psychiatry] 2024 Oct 22; Vol. 136, pp. 111174. Date of Electronic Publication: 2024 Oct 22.
DOI: 10.1016/j.pnpbp.2024.111174
Abstrakt: Background: Prenatal alcohol exposure (PAE) induces a wide range of neurodevelopmental disabilities that are grouped under the term 'fetal alcohol spectrum disorders' (FASD). The effects of PAE on brain development are dependent on complex neurochemical events, including modification of AMPA receptors (AMPARs). We have recently found that chronic ethanol (EtOH) exposure decreases AMPA-mediated neurotransmission and expression through the overexpression of the specific microRNA (miR)137 and 501-3p, which target GluA1 AMPA subunit, in the developing hippocampus in vitro. Here, we explored how PAE mice may alter AMPAergic synapses in the hippocampus, and its effects on behavior.
Methods: To model PAE, we exposed C57Bl/6 pregnant mice to 10 % EtOH during during the first 10 days of gestation (GD 0-10; equivalent to the first trimester of pregnancy in humans). AMPA subunits postsynaptic expression in the hippocampus, electrical properties of CA1 neurons, memory recognition, and locomotor functions were then analyzed in adolescent PAE-exposed offspring.
Results: PAE adolescent mice showed dysregulation of AMPAergic neurotransmission, and increased miR 501-3p expression, associated with a significant reduction of spontaneous AMPA currents and intrinsic somatic excitability. In addition, PAE reduced the phosphorylation of AMPAR-containing GluA1 subunit, despite an increase in its total levels. Of note, the total levels of GluA2 and GluA3 AMPA receptors were enhanced as well. Consistently, at behavioral level, PAE reduced object recognition without altering locomotor activity.
Conclusions: Our study shows that PAE leads to dysfunctional formation of AMPAergic synapses that could be responsible for neurobehavioral impairments, contributing to the understanding of the pathogenesis of FASD.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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