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Cited by 79Genetics and Neurodevelopmental DisordersAutism Spectrum Disorder ResearchNeuroscience and Neuropharmacology Research

Evidence of reactive astrocytes but not peripheral immune system activation in a mouse model of Fragile X syndrome.

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Yuskaitis, Christopher J., Beurel, Eleonore, Jope, Richard S.·2010·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
DOI 10.1016/j.bbadis.2010.06.015PMC PMC2942952
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Abstract

Fragile X syndrome (FXS) is the most common form of inherited mental retardation and is one of the few known genetic causes of autism. FXS results from the loss of Fmr1 gene function; thus, Fmr1 knockout mice provide a model to study impairments associated with FXS and autism and to test potential therapeutic interventions. The inhibitory serine phosphorylation of glycogen synthase kinase-3 (GSK3) is lower in brain regions of Fmr1 knockout mice than wild-type mice and the GSK3 inhibitor lithium rescues several behavioral impairments in Fmr1 knockout mice. Therefore, we examined if the serine phosphorylation of GSK3 in Fmr1 knockout mice also was altered outside the brain and if administration of lithium ameliorated the macroorchidism phenotype. Additionally, since GSK3 regulates numerous functions of the immune system and immune alterations have been associated with autism, we tested if immune function is altered in Fmr1 knockout mice. The inhibitory serine phosphorylation of GSK3 was significantly lower in the testis and liver of Fmr1 knockout mice than wild-type mice, and chronic lithium treatment reduced macroorchidism in Fmr1 knockout mice. No alterations in peripheral immune function were identified in Fmr1 knockout mice. However, examination of glia, the immune cells of the brain, revealed reactive astrocytes in several brain regions of Fmr1 knockout mice and treatment with lithium reduced this in the striatum and cerebellum. These results provide further evidence of the involvement of dysregulated GSK3 in FXS, and demonstrate that lithium administration reduces macroorchidism and reactive astrocytes in Fmr1 knockout mice.

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  • Astrocytes with abnormally high GFAP have been observed in striatal, hippocampal, cortical, and cerebellar areas of adult Fmr1 KO mice.

    “Astrocytes with abnormally high GFAP, have been observed in striatal, hippocampal, cortical, and cerebellar areas of adult Fmr1 KO mice (Yuskaitis et al., 2010; Pacey et al., 2015).”

    From Astrocytes in fragile X syndrome (2024) · cites this paper as Yuskaitis et al., 2010

    Results §3.5 reports significantly elevated GFAP in the striatum, hippocampus, and cerebral cortex of Fmr1 knockout mice. The Discussion explicitly says the increase was not found in the cerebellum, so this source does not support the fourth region in the citing sentence. (LLM, conf=0.94)

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References 57 · Cited by 79

Research works printed but not linked: 42

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Authors
Yuskaitis, C. J., Beurel, E., & Jope, R. S.
Affiliations
University of Alabama at Birmingham (US)
Corresponding author
Jope, Richard S.
ORCID
Yuskaitis, Christopher J.
Venue
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Publisher
Elsevier BV
Published
2010-11
Volume
1802
Issue
11
Pages
1006-1012
ISSN
0925-4439 (ISSN-L)
DOI
10.1016/j.bbadis.2010.06.015
PMC
PMC2942952
OpenAlex
W2165648215
Cited by
79
References
57
Citations by year
2026: 3 · 2025: 1 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 5 · 2018: 2 · 2017: 5 · 2016: 5 · 2015: 10 · 2014: 12 · 2013: 6 · 2012: 2
FWCI
3.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion, other-oa)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Funders
  • NIH Neuroscience Blueprint Core
  • FRAXA Research Foundation
  • NIH (MH38752)
  • NARSAD
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
fragile X syndrome, Fmr1 knockout mice, glycogen synthase kinase-3, lithium, reactive astrocytes, macroorchidism, autism spectrum disorder, testis, liver, striatum, cerebellum, glia
MeSH terms
Animals, Astrocytes, Brain, Disease Models, Animal, Female, Fragile X Syndrome, Glial Fibrillary Acidic Protein, Immune System, Male, Mice, Inbred C57BL, Phosphorylation, Serine, Testis, Immunoblotting, Cytokines, Lithium Carbonate, Microglia, Mice, Knockout, Glycogen Synthase Kinase 3, Mice, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1

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