title: Expression of fragile X mental retardation protein in neurons and glia of the developing and adult mouse brain.
abstract: Fragile X syndrome is the most common inherited form of mental retardation and autism. It is caused by a reduction or elimination of the expression of fragile X mental retardation protein (FMRP). Because fragile X syndrome is a neurodevelopmental disorder, it is important to fully document the cell type expression in the developing CNS to provide a better understanding of the molecular function of FMRP, and the pathogenesis of the syndrome. We investigated FMRP expression in the brain using double-labeling immunocytochemistry and cell type markers for neurons (NeuN), astrocytes (S100β), microglia (Iba-1), and oligodendrocyte precursor cells (NG2). The hippocampus, striatum, cingulate cortex, retrosplenial cortex, corpus callosum and cerebellum were assessed in wild-type C57/BL6 mice at postnatal days 0, 10, 20, and adult. Our results demonstrate that FMRP is ubiquitously expressed in neurons at all times and brain regions studied, except for corpus callosum where FMRP was predominantly present in astrocytes at all ages. FMRP expression in Iba-1 and NG2-positive cells was detected at postnatal day 0 and 10 and gradually decreased to very low or undetectable levels in postnatal day 20 and adult mice. Our results reveal that in addition to continuous and extensive expression in neurons in the immature and mature brain, FMRP is also present in astrocytes, oligodendrocyte precursor cells, and microglia during the early and mid-postnatal developmental stages of brain maturation. Prominent expression of FMRP in glia during these crucial stages of brain development suggests an important contribution to normal brain function, and in its absence, to the fragile X phenotype.
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, and; S.H and S.G. contributed equally to this work.
authors.forename: Shervin
authors.initials: S
authors.lastname: Gholizadeh
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, and; S.H and S.G. contributed equally to this work.
authors.forename: Sebok Kumar
authors.initials: SK
authors.lastname: Halder
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, and; Department of Pharmacology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: d.hampson@utoronto.ca.
authors.forename: David R
authors.initials: DR
authors.lastname: Hampson
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D001921:Brain / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D002135:Calcium-Binding Proteins / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D002135:Calcium-Binding Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D008840:Microfilament Proteins; D010751:Phosphopyruvate Hydratase; D011509:Proteoglycans; D064568:S100 Calcium Binding Protein beta Subunit; D000099216:Chondroitin Sulfate Proteoglycan 4; C491049:Aif1 protein, mouse
keywords: Astrocytes; Microglia; NG2; Neurons; Oligodendrocyte precursor cells; Oligodendrocytes; Postnatal development; S100β