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

Christopher J. Yuskaitis, Eleonore Beurel, Richard S. Jope

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1006-1012
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1802
Issue number11
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

Keywords

  • Astrocytes
  • Fragile X syndrome
  • Glycogen synthase kinase-3
  • Lithium
  • Macroorchidism

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

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