Sex Differences in Dopamine Receptor Signaling in <i>Fmr1</i> Knockout Mice: A Pilot Study

Fragile X syndrome (FXS) is an X-chromosome-linked dominant genetic disorder that causes a variable degree of cognitive dysfunction and developmental disability. Current treatment is symptomatic and no existing medications target the specific cause of FXS. As with other X-linked disorders, FXS manif...

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Autores principales:	Anlong Jiang, Le Wang, Justin Y. D. Lu, Amy Freeman, Charlie Campbell, Ping Su, Albert H. C. Wong, Fang Liu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Fragile X syndrome sex difference L-stepholidine dopamine signaling <i>Fmr1</i> knockout D1 receptor Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/4d31ac84f8ca48baabd3a110d5c4cedf
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spelling	oai:doaj.org-article:4d31ac84f8ca48baabd3a110d5c4cedf2021-11-25T16:56:33ZSex Differences in Dopamine Receptor Signaling in <i>Fmr1</i> Knockout Mice: A Pilot Study10.3390/brainsci111113982076-3425https://doaj.org/article/4d31ac84f8ca48baabd3a110d5c4cedf2021-10-01T00:00:00Zhttps://www.mdpi.com/2076-3425/11/11/1398https://doaj.org/toc/2076-3425Fragile X syndrome (FXS) is an X-chromosome-linked dominant genetic disorder that causes a variable degree of cognitive dysfunction and developmental disability. Current treatment is symptomatic and no existing medications target the specific cause of FXS. As with other X-linked disorders, FXS manifests differently in males and females, including abnormalities in the dopamine system that are also seen in <i>Fmr1</i>-knockout (KO) mice. We investigated sex differences in dopamine signaling in <i>Fmr1</i>-KO mice in response to L-stepholidine, a dopamine D1 receptor agonist and D2 receptor antagonist. We found significant sex differences in basal levels of phosphorylated protein kinase A (p-PKA) and glycogen synthase kinase (GSK)-3β in wild type mice that were absent in <i>Fmr1</i>-KO mice. In wild-type mice, L-stepholidine increased p-PKA in males but not female mice, decreased p-GSK-3 in female mice and increased p-GSK-3 in male mice. Conversely, in <i>Fmr1</i>-KO mice, L-stepholidine increased p-PKA and p-GSK-3β in females, and decreased p-PKA and p-GSK-3β in males.Anlong JiangLe WangJustin Y. D. LuAmy FreemanCharlie CampbellPing SuAlbert H. C. WongFang LiuMDPI AGarticleFragile X syndromesex differenceL-stepholidinedopamine signaling<i>Fmr1</i> knockoutD1 receptorNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENBrain Sciences, Vol 11, Iss 1398, p 1398 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Fragile X syndrome sex difference L-stepholidine dopamine signaling <i>Fmr1</i> knockout D1 receptor Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Fragile X syndrome sex difference L-stepholidine dopamine signaling <i>Fmr1</i> knockout D1 receptor Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Anlong Jiang Le Wang Justin Y. D. Lu Amy Freeman Charlie Campbell Ping Su Albert H. C. Wong Fang Liu Sex Differences in Dopamine Receptor Signaling in <i>Fmr1</i> Knockout Mice: A Pilot Study
description	Fragile X syndrome (FXS) is an X-chromosome-linked dominant genetic disorder that causes a variable degree of cognitive dysfunction and developmental disability. Current treatment is symptomatic and no existing medications target the specific cause of FXS. As with other X-linked disorders, FXS manifests differently in males and females, including abnormalities in the dopamine system that are also seen in <i>Fmr1</i>-knockout (KO) mice. We investigated sex differences in dopamine signaling in <i>Fmr1</i>-KO mice in response to L-stepholidine, a dopamine D1 receptor agonist and D2 receptor antagonist. We found significant sex differences in basal levels of phosphorylated protein kinase A (p-PKA) and glycogen synthase kinase (GSK)-3β in wild type mice that were absent in <i>Fmr1</i>-KO mice. In wild-type mice, L-stepholidine increased p-PKA in males but not female mice, decreased p-GSK-3 in female mice and increased p-GSK-3 in male mice. Conversely, in <i>Fmr1</i>-KO mice, L-stepholidine increased p-PKA and p-GSK-3β in females, and decreased p-PKA and p-GSK-3β in males.
format	article
author	Anlong Jiang Le Wang Justin Y. D. Lu Amy Freeman Charlie Campbell Ping Su Albert H. C. Wong Fang Liu
author_facet	Anlong Jiang Le Wang Justin Y. D. Lu Amy Freeman Charlie Campbell Ping Su Albert H. C. Wong Fang Liu
author_sort	Anlong Jiang
title	Sex Differences in Dopamine Receptor Signaling in <i>Fmr1</i> Knockout Mice: A Pilot Study
title_short	Sex Differences in Dopamine Receptor Signaling in <i>Fmr1</i> Knockout Mice: A Pilot Study
title_full	Sex Differences in Dopamine Receptor Signaling in <i>Fmr1</i> Knockout Mice: A Pilot Study
title_fullStr	Sex Differences in Dopamine Receptor Signaling in <i>Fmr1</i> Knockout Mice: A Pilot Study
title_full_unstemmed	Sex Differences in Dopamine Receptor Signaling in <i>Fmr1</i> Knockout Mice: A Pilot Study
title_sort	sex differences in dopamine receptor signaling in <i>fmr1</i> knockout mice: a pilot study
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/4d31ac84f8ca48baabd3a110d5c4cedf
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Sex Differences in Dopamine Receptor Signaling in <i>Fmr1</i> Knockout Mice: A Pilot Study

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