title: MeCP2 regulates GFAP expression within the developing brain.
abstract: Mutations in MECP2 cause Rett syndrome (RTT), an X-linked neurodevelopmental disorder that primarily affects females. Individuals with RTT have increased glial fibrillary acidic protein (GFAP) expression in the brain. GFAP is an intermediate filament protein that is expressed predominately within astrocytes in the CNS. MeCP2 binds to methylated regions of the GFAP promoter region and suppresses GFAP expression in vitro. Therefore, we wanted to determine if transiently reducing MeCP2 expression would increase GFAP expression in the developing rat brain. Male and female rats received infusions of either MeCP2 or control siRNA targeting the amygdala during the first 3 days of postnatal life. Brains were collected after 6h or 2 weeks following the last infusion. MeCP2 siRNA increased GFAP mRNA and protein within the female, but not the male, amygdala on postnatal day (PN) 2. Two weeks following the infusion, levels returned to normal. MeCP2 siRNA targeting the hypothalamus also increases GFAP mRNA within the female hypothalamus on PN2, suggesting that the regulation is not brain region-specific. It appears that MeCP2 does not regulate all astrocyte markers in the developing female brain, but specifically regulates GFAP expression, as levels of S100β and vimentin were not altered in the female amygdala at either time point. These data contribute to the idea that the role of MeCP2 differs in the developing male versus female brain. Further elucidating the regulation and function of GFAP can contribute to our understanding of MeCP2 function and perhaps RTT etiology.
authors.affiliation: Department of Psychology, 1202 West Johnson Street, University of Wisconsin-Madison, Madison, WI 53706-1969, USA. Electronic address: forbeslorman@wisc.edu.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Forbes-Lorman
authors.affiliation: Wisconsin National Primate Research Center, 1220 Capitol Court, University of Wisconsin-Madison, Madison, WI 53715, USA. Electronic address: jrkurian@wisc.edu.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Kurian
authors.affiliation: Department of Psychology, 1202 West Johnson Street, University of Wisconsin-Madison, Madison, WI 53706-1969, USA; Neuroscience Training Program, 1300 University Avenue, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: apauger@wisc.edu.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Auger
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064568:S100 Calcium Binding Protein beta Subunit / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; C497394:Mecp2 protein, rat; D051783:Methyl-CpG-Binding Protein 2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D064568:S100 Calcium Binding Protein beta Subunit; D014746:Vimentin; D007041:Hypoxanthine Phosphoribosyltransferase
keywords: Development; GFAP; MeCP2; Sex differences