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Gestational ethanol exposure impairs motor skills in female mice through dysregulated striatal dopamine and acetylcholine function

Fetal alcohol exposure has deleterious consequences on the motor skills of patients affected by Fetal Alcohol Spectrum Disorder (FASD) and in pre-clinical models of gestational ethanol exposure (GEE). Deficits in striatal cholinergic interneurons (CINs) and dopamine function impair action learning a...

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Autores principales: Bariselli, Sebastiano, Mateo, Yolanda, Reuveni, Noa, Lovinger, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10579353/
https://www.ncbi.nlm.nih.gov/pubmed/37188849
http://dx.doi.org/10.1038/s41386-023-01594-4
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author Bariselli, Sebastiano
Mateo, Yolanda
Reuveni, Noa
Lovinger, David M.
author_facet Bariselli, Sebastiano
Mateo, Yolanda
Reuveni, Noa
Lovinger, David M.
author_sort Bariselli, Sebastiano
collection PubMed
description Fetal alcohol exposure has deleterious consequences on the motor skills of patients affected by Fetal Alcohol Spectrum Disorder (FASD) and in pre-clinical models of gestational ethanol exposure (GEE). Deficits in striatal cholinergic interneurons (CINs) and dopamine function impair action learning and execution, yet the effects of GEE on acetylcholine (ACh) and striatal dopamine release remain unexplored. Here, we report that alcohol exposure during the first ten postnatal days (GEE(P0-P10)), which mimics ethanol consumption during the last gestational trimester in humans, induces sex-specific anatomical and motor skill deficits in female mice during adulthood. Consistent with these behavioral impairments, we observed increased stimulus evoked-dopamine levels in the dorsolateral striatum (DLS) of GEE(P0-P10) female, but not male, mice. Further experiments revealed sex-specific deficits in β2-containing nicotinic ACh receptor (nAChR)-modulation of electrically evoked dopamine release. Moreover, we found a reduced decay of ACh transients and a decreased excitability of striatal CINs in DLS of GEE(P0-P10) females, indicating striatal CIN dysfunctions. Finally, the administration of varenicline, a β2-containing nAChR partial agonist, and chemogenetic-mediated increase in CIN activity improved motor performance in adult GEE(P0-P10) females. Altogether, these data shed new light on GEE-induced striatal deficits and establish potential pharmacological and circuit-specific interventions to ameliorate motor symptoms of FASD.
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spelling pubmed-105793532023-10-18 Gestational ethanol exposure impairs motor skills in female mice through dysregulated striatal dopamine and acetylcholine function Bariselli, Sebastiano Mateo, Yolanda Reuveni, Noa Lovinger, David M. Neuropsychopharmacology Article Fetal alcohol exposure has deleterious consequences on the motor skills of patients affected by Fetal Alcohol Spectrum Disorder (FASD) and in pre-clinical models of gestational ethanol exposure (GEE). Deficits in striatal cholinergic interneurons (CINs) and dopamine function impair action learning and execution, yet the effects of GEE on acetylcholine (ACh) and striatal dopamine release remain unexplored. Here, we report that alcohol exposure during the first ten postnatal days (GEE(P0-P10)), which mimics ethanol consumption during the last gestational trimester in humans, induces sex-specific anatomical and motor skill deficits in female mice during adulthood. Consistent with these behavioral impairments, we observed increased stimulus evoked-dopamine levels in the dorsolateral striatum (DLS) of GEE(P0-P10) female, but not male, mice. Further experiments revealed sex-specific deficits in β2-containing nicotinic ACh receptor (nAChR)-modulation of electrically evoked dopamine release. Moreover, we found a reduced decay of ACh transients and a decreased excitability of striatal CINs in DLS of GEE(P0-P10) females, indicating striatal CIN dysfunctions. Finally, the administration of varenicline, a β2-containing nAChR partial agonist, and chemogenetic-mediated increase in CIN activity improved motor performance in adult GEE(P0-P10) females. Altogether, these data shed new light on GEE-induced striatal deficits and establish potential pharmacological and circuit-specific interventions to ameliorate motor symptoms of FASD. Springer International Publishing 2023-05-15 2023-11 /pmc/articles/PMC10579353/ /pubmed/37188849 http://dx.doi.org/10.1038/s41386-023-01594-4 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bariselli, Sebastiano
Mateo, Yolanda
Reuveni, Noa
Lovinger, David M.
Gestational ethanol exposure impairs motor skills in female mice through dysregulated striatal dopamine and acetylcholine function
title Gestational ethanol exposure impairs motor skills in female mice through dysregulated striatal dopamine and acetylcholine function
title_full Gestational ethanol exposure impairs motor skills in female mice through dysregulated striatal dopamine and acetylcholine function
title_fullStr Gestational ethanol exposure impairs motor skills in female mice through dysregulated striatal dopamine and acetylcholine function
title_full_unstemmed Gestational ethanol exposure impairs motor skills in female mice through dysregulated striatal dopamine and acetylcholine function
title_short Gestational ethanol exposure impairs motor skills in female mice through dysregulated striatal dopamine and acetylcholine function
title_sort gestational ethanol exposure impairs motor skills in female mice through dysregulated striatal dopamine and acetylcholine function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10579353/
https://www.ncbi.nlm.nih.gov/pubmed/37188849
http://dx.doi.org/10.1038/s41386-023-01594-4
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