Fluoxetine increases brain MeCP2 immuno-positive cells in a female Mecp2 heterozygous mouse model of Rett syndrome through endogenous serotonin

Abstract Motor skill deficit is a common and invalidating symptom of Rett syndrome (RTT), a rare disease almost exclusively affecting girls during the first/second year of life. Loss-of-function mutations of the methyl-CpG-binding protein2 (MECP2; Mecp2 in rodents) gene is the cause in most patients...

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Autores principales:	Claudia Villani, Mirjana Carli, Anna Maria Castaldo, Giuseppina Sacchetti, Roberto William Invernizzi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9a69fff8c1234c6e915bdf957562a834
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spelling	oai:doaj.org-article:9a69fff8c1234c6e915bdf957562a8342021-12-02T16:26:22ZFluoxetine increases brain MeCP2 immuno-positive cells in a female Mecp2 heterozygous mouse model of Rett syndrome through endogenous serotonin10.1038/s41598-021-94156-x2045-2322https://doaj.org/article/9a69fff8c1234c6e915bdf957562a8342021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94156-xhttps://doaj.org/toc/2045-2322Abstract Motor skill deficit is a common and invalidating symptom of Rett syndrome (RTT), a rare disease almost exclusively affecting girls during the first/second year of life. Loss-of-function mutations of the methyl-CpG-binding protein2 (MECP2; Mecp2 in rodents) gene is the cause in most patients. We recently found that fluoxetine, a selective serotonin (5-HT) reuptake inhibitor and antidepressant drug, fully rescued motor coordination deficits in Mecp2 heterozygous (Mecp2 HET) mice acting through brain 5-HT. Here, we asked whether fluoxetine could increase MeCP2 expression in the brain of Mecp2 HET mice, under the same schedule of treatment improving motor coordination. Fluoxetine increased the number of MeCP2 immuno-positive (MeCP2+) cells in the prefrontal cortex, M1 and M2 motor cortices, and in dorsal, ventral and lateral striatum. Fluoxetine had no effect in the CA3 region of the hippocampus or in any of the brain regions of WT mice. Inhibition of 5-HT synthesis abolished the fluoxetine-induced rise of MeCP2+ cells. These findings suggest that boosting 5-HT transmission is sufficient to enhance the expression of MeCP2 in several brain regions of Mecp2 HET mice. Fluoxetine-induced rise of MeCP2 could potentially rescue motor coordination and other deficits of RTT.Claudia VillaniMirjana CarliAnna Maria CastaldoGiuseppina SacchettiRoberto William InvernizziNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Claudia Villani Mirjana Carli Anna Maria Castaldo Giuseppina Sacchetti Roberto William Invernizzi Fluoxetine increases brain MeCP2 immuno-positive cells in a female Mecp2 heterozygous mouse model of Rett syndrome through endogenous serotonin
description	Abstract Motor skill deficit is a common and invalidating symptom of Rett syndrome (RTT), a rare disease almost exclusively affecting girls during the first/second year of life. Loss-of-function mutations of the methyl-CpG-binding protein2 (MECP2; Mecp2 in rodents) gene is the cause in most patients. We recently found that fluoxetine, a selective serotonin (5-HT) reuptake inhibitor and antidepressant drug, fully rescued motor coordination deficits in Mecp2 heterozygous (Mecp2 HET) mice acting through brain 5-HT. Here, we asked whether fluoxetine could increase MeCP2 expression in the brain of Mecp2 HET mice, under the same schedule of treatment improving motor coordination. Fluoxetine increased the number of MeCP2 immuno-positive (MeCP2+) cells in the prefrontal cortex, M1 and M2 motor cortices, and in dorsal, ventral and lateral striatum. Fluoxetine had no effect in the CA3 region of the hippocampus or in any of the brain regions of WT mice. Inhibition of 5-HT synthesis abolished the fluoxetine-induced rise of MeCP2+ cells. These findings suggest that boosting 5-HT transmission is sufficient to enhance the expression of MeCP2 in several brain regions of Mecp2 HET mice. Fluoxetine-induced rise of MeCP2 could potentially rescue motor coordination and other deficits of RTT.
format	article
author	Claudia Villani Mirjana Carli Anna Maria Castaldo Giuseppina Sacchetti Roberto William Invernizzi
author_facet	Claudia Villani Mirjana Carli Anna Maria Castaldo Giuseppina Sacchetti Roberto William Invernizzi
author_sort	Claudia Villani
title	Fluoxetine increases brain MeCP2 immuno-positive cells in a female Mecp2 heterozygous mouse model of Rett syndrome through endogenous serotonin
title_short	Fluoxetine increases brain MeCP2 immuno-positive cells in a female Mecp2 heterozygous mouse model of Rett syndrome through endogenous serotonin
title_full	Fluoxetine increases brain MeCP2 immuno-positive cells in a female Mecp2 heterozygous mouse model of Rett syndrome through endogenous serotonin
title_fullStr	Fluoxetine increases brain MeCP2 immuno-positive cells in a female Mecp2 heterozygous mouse model of Rett syndrome through endogenous serotonin
title_full_unstemmed	Fluoxetine increases brain MeCP2 immuno-positive cells in a female Mecp2 heterozygous mouse model of Rett syndrome through endogenous serotonin
title_sort	fluoxetine increases brain mecp2 immuno-positive cells in a female mecp2 heterozygous mouse model of rett syndrome through endogenous serotonin
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9a69fff8c1234c6e915bdf957562a834
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Fluoxetine increases brain MeCP2 immuno-positive cells in a female Mecp2 heterozygous mouse model of Rett syndrome through endogenous serotonin

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