title: Persistent astrocyte activation in the fragile X mouse cerebellum.
abstract: BACKGROUND
  Fragile X Syndrome, the most common single gene cause of autism, results from loss of the RNA-binding protein FMRP. Although FMRP is highly expressed in neurons, it has also recently been identified in glia. It has been postulated that in the absence of FMRP, abnormal function of non-neuronal cells may contribute to the pathogenesis of the disorder. We previously demonstrated reduced numbers of oligodendrocyte precursor cells and delayed myelination in the cerebellum of fragile X (Fmr1) knockout mice.
  
  
  METHODS
  We used quantitative western blotting and immunocytochemistry to examine the status of astrocytes and microglia in the cerebellum of Fmr1 mice during development and in adulthood.
  
  
  RESULTS
  We report increased expression of the astrocyte marker GFAP in the cerebellum of Fmr1 mice starting in the second postnatal week and persisting in to adulthood. At 2 weeks postnatal, expression of Tumor Necrosis Factor Receptor 2 (TNFR2) and Leukemia Inhibitory Factor (LIF) were elevated in the Fmr1 KO cerebellum. In adults, expression of TNFR2 and the glial marker S100β were also elevated in Fmr1 knockouts, but LIF expression was not different from wild-type mice. We found no evidence of microglial activation or neuroinflammation at any age examined.
  
  
  CONCLUSIONS
  These findings demonstrate an atypical pattern of astrogliosis in the absence of microglial activation in Fmr1 knockout mouse cerebellum. Enhanced TNFR2 and LIF expression in young mice suggests that changes in the expression of astrocytic proteins may be an attempt to compensate for delayed myelination in the developing cerebellum of Fmr1 mice.
authors.affiliation: Department of Pharmaceutical Sciences Leslie Dan Faculty of Pharmacy University of Toronto 144 College Street Toronto Ontario Canada M5S 3M2.
authors.forename: Laura K K
authors.initials: LK
authors.lastname: Pacey
authors.affiliation: Department of Pharmaceutical Sciences Leslie Dan Faculty of Pharmacy University of Toronto 144 College Street Toronto Ontario Canada M5S 3M2.
authors.forename: Sihui
authors.initials: S
authors.lastname: Guan
authors.affiliation: Department of Pharmaceutical Sciences Leslie Dan Faculty of Pharmacy University of Toronto 144 College Street Toronto Ontario Canada M5S 3M2.
authors.forename: Sujeenthar
authors.initials: S
authors.lastname: Tharmalingam
authors.affiliation: Department of Neuroinflammation Lundbeck Research USA 215 College Road Paramus New Jersey 07652.
authors.forename: Christian
authors.initials: C
authors.lastname: Thomsen
authors.affiliation: Department of Pharmaceutical Sciences Leslie Dan Faculty of Pharmacy University of Toronto 144 College Street Toronto Ontario Canada M5S 3M2 ; Department of Pharmacology Faculty of Medicine University of Toronto 144 College Street Toronto Ontario Canada M5S 3M2.
authors.forename: David R
authors.initials: DR
authors.lastname: Hampson
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D001321:Autistic Disorder / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism; D005600:Fragile X Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497684:Fmr1 protein, mouse
keywords: Astrogliosis; FMRP; GFAP; LIF; S100B; TNFR2; autism; myelin; oligodendrocyte precursor cells