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Sex Differences in Dopamine Receptor Signaling in Fmr1 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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615700/ https://www.ncbi.nlm.nih.gov/pubmed/34827397 http://dx.doi.org/10.3390/brainsci11111398 |
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author | Jiang, Anlong Wang, Le Lu, Justin Y. D. Freeman, Amy Campbell, Charlie Su, Ping Wong, Albert H. C. Liu, Fang |
author_facet | Jiang, Anlong Wang, Le Lu, Justin Y. D. Freeman, Amy Campbell, Charlie Su, Ping Wong, Albert H. C. Liu, Fang |
author_sort | Jiang, Anlong |
collection | PubMed |
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 Fmr1-knockout (KO) mice. We investigated sex differences in dopamine signaling in Fmr1-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 Fmr1-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 Fmr1-KO mice, L-stepholidine increased p-PKA and p-GSK-3β in females, and decreased p-PKA and p-GSK-3β in males. |
format | Online Article Text |
id | pubmed-8615700 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86157002021-11-26 Sex Differences in Dopamine Receptor Signaling in Fmr1 Knockout Mice: A Pilot Study Jiang, Anlong Wang, Le Lu, Justin Y. D. Freeman, Amy Campbell, Charlie Su, Ping Wong, Albert H. C. Liu, Fang Brain Sci Article 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 Fmr1-knockout (KO) mice. We investigated sex differences in dopamine signaling in Fmr1-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 Fmr1-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 Fmr1-KO mice, L-stepholidine increased p-PKA and p-GSK-3β in females, and decreased p-PKA and p-GSK-3β in males. MDPI 2021-10-24 /pmc/articles/PMC8615700/ /pubmed/34827397 http://dx.doi.org/10.3390/brainsci11111398 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jiang, Anlong Wang, Le Lu, Justin Y. D. Freeman, Amy Campbell, Charlie Su, Ping Wong, Albert H. C. Liu, Fang Sex Differences in Dopamine Receptor Signaling in Fmr1 Knockout Mice: A Pilot Study |
title | Sex Differences in Dopamine Receptor Signaling in Fmr1 Knockout Mice: A Pilot Study |
title_full | Sex Differences in Dopamine Receptor Signaling in Fmr1 Knockout Mice: A Pilot Study |
title_fullStr | Sex Differences in Dopamine Receptor Signaling in Fmr1 Knockout Mice: A Pilot Study |
title_full_unstemmed | Sex Differences in Dopamine Receptor Signaling in Fmr1 Knockout Mice: A Pilot Study |
title_short | Sex Differences in Dopamine Receptor Signaling in Fmr1 Knockout Mice: A Pilot Study |
title_sort | sex differences in dopamine receptor signaling in fmr1 knockout mice: a pilot study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615700/ https://www.ncbi.nlm.nih.gov/pubmed/34827397 http://dx.doi.org/10.3390/brainsci11111398 |
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