Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Jiang, Anlong, Wang, Le, Lu, Justin Y. D., Freeman, Amy, Campbell, Charlie, Su, Ping, Wong, Albert H. C., Liu, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1784604168087928832
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
work_keys_str_mv AT jianganlong sexdifferencesindopaminereceptorsignalinginfmr1knockoutmiceapilotstudy
AT wangle sexdifferencesindopaminereceptorsignalinginfmr1knockoutmiceapilotstudy
AT lujustinyd sexdifferencesindopaminereceptorsignalinginfmr1knockoutmiceapilotstudy
AT freemanamy sexdifferencesindopaminereceptorsignalinginfmr1knockoutmiceapilotstudy
AT campbellcharlie sexdifferencesindopaminereceptorsignalinginfmr1knockoutmiceapilotstudy
AT suping sexdifferencesindopaminereceptorsignalinginfmr1knockoutmiceapilotstudy
AT wongalberthc sexdifferencesindopaminereceptorsignalinginfmr1knockoutmiceapilotstudy
AT liufang sexdifferencesindopaminereceptorsignalinginfmr1knockoutmiceapilotstudy