Lithium reverses increased rates of cerebral protein synthesis in a mouse model of fragile X syndrome
Individuals with fragile X syndrome (FXS), an inherited form of cognitive disability, have a wide range of symptoms including hyperactivity, autistic behavior, seizures and learning deficits. FXS is caused by silencing of FMR1 and the consequent absence of fragile X mental retardation protein (FMRP)...
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doaj-ad566c7aaf48402ab984c39ef28136792021-03-22T12:38:00ZengElsevierNeurobiology of Disease1095-953X2012-03-0145311451152Lithium reverses increased rates of cerebral protein synthesis in a mouse model of fragile X syndromeZhong-Hua Liu0Tianjian Huang1Carolyn Beebe Smith2Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USASection on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USACorresponding author at: Section on Neuroadaptation and Protein Metabolism, Bldg. 10, 2D54, 10 Center Drive, National Institutes of Health, Bethesda, MD 20892-1298, USA. Fax: +1 301 480 1668.; Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USAIndividuals with fragile X syndrome (FXS), an inherited form of cognitive disability, have a wide range of symptoms including hyperactivity, autistic behavior, seizures and learning deficits. FXS is caused by silencing of FMR1 and the consequent absence of fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that associates with polyribosomes and negatively regulates translation. In a previous study of a mouse model of FXS (Fmr1 knockout (KO)) we demonstrated that in vivo rates of cerebral protein synthesis (rCPS) were elevated in selective brain regions suggesting that the absence of FMRP in FXS may result in dysregulation of cerebral protein synthesis. Lithium, a drug used clinically to treat bipolar disorder, has been used to improve mood dysregulation in individuals with FXS. We reported previously that in the Fmr1 KO mouse chronic dietary lithium treatment reversed or ameliorated both behavioral and morphological abnormalities. Herein we report that chronic dietary lithium treatment reversed the increased rCPS in Fmr1 KO mice with little effect on wild type mice. We also report our results of analyses of key signaling molecules involved in regulation of mRNA translation. Our analyses indicate that neither effects on the PI3K/Akt nor the MAPK/ERK 1/2 pathway fully account for the effects of lithium treatment on rCPS. Collectively our findings and those from other laboratories on the efficacy of lithium treatment in animal models support further studies in patients with FXS.http://www.sciencedirect.com/science/article/pii/S0969996111004128Protein synthesisFragile X syndromeLithiumFmr1MouseBrain |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhong-Hua Liu Tianjian Huang Carolyn Beebe Smith |
spellingShingle |
Zhong-Hua Liu Tianjian Huang Carolyn Beebe Smith Lithium reverses increased rates of cerebral protein synthesis in a mouse model of fragile X syndrome Neurobiology of Disease Protein synthesis Fragile X syndrome Lithium Fmr1 Mouse Brain |
author_facet |
Zhong-Hua Liu Tianjian Huang Carolyn Beebe Smith |
author_sort |
Zhong-Hua Liu |
title |
Lithium reverses increased rates of cerebral protein synthesis in a mouse model of fragile X syndrome |
title_short |
Lithium reverses increased rates of cerebral protein synthesis in a mouse model of fragile X syndrome |
title_full |
Lithium reverses increased rates of cerebral protein synthesis in a mouse model of fragile X syndrome |
title_fullStr |
Lithium reverses increased rates of cerebral protein synthesis in a mouse model of fragile X syndrome |
title_full_unstemmed |
Lithium reverses increased rates of cerebral protein synthesis in a mouse model of fragile X syndrome |
title_sort |
lithium reverses increased rates of cerebral protein synthesis in a mouse model of fragile x syndrome |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2012-03-01 |
description |
Individuals with fragile X syndrome (FXS), an inherited form of cognitive disability, have a wide range of symptoms including hyperactivity, autistic behavior, seizures and learning deficits. FXS is caused by silencing of FMR1 and the consequent absence of fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that associates with polyribosomes and negatively regulates translation. In a previous study of a mouse model of FXS (Fmr1 knockout (KO)) we demonstrated that in vivo rates of cerebral protein synthesis (rCPS) were elevated in selective brain regions suggesting that the absence of FMRP in FXS may result in dysregulation of cerebral protein synthesis. Lithium, a drug used clinically to treat bipolar disorder, has been used to improve mood dysregulation in individuals with FXS. We reported previously that in the Fmr1 KO mouse chronic dietary lithium treatment reversed or ameliorated both behavioral and morphological abnormalities. Herein we report that chronic dietary lithium treatment reversed the increased rCPS in Fmr1 KO mice with little effect on wild type mice. We also report our results of analyses of key signaling molecules involved in regulation of mRNA translation. Our analyses indicate that neither effects on the PI3K/Akt nor the MAPK/ERK 1/2 pathway fully account for the effects of lithium treatment on rCPS. Collectively our findings and those from other laboratories on the efficacy of lithium treatment in animal models support further studies in patients with FXS. |
topic |
Protein synthesis Fragile X syndrome Lithium Fmr1 Mouse Brain |
url |
http://www.sciencedirect.com/science/article/pii/S0969996111004128 |
work_keys_str_mv |
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