title: Memory impairment induced by brain iron overload is accompanied by reduced H3K9 acetylation and ameliorated by sodium butyrate.
abstract: Iron accumulation in the brain has been associated to the pathogenesis of neurodegenerative disorders. We have previously demonstrated that iron overload in the neonatal period results in severe and persistent memory deficits in adult rats. Alterations in histone acetylation have been associated with memory deficits in models of neurological disorders. Here we examine histone acetylation in the brain and the effects of the histone deacetylase inhibitor (HDACi) sodium butyrate (NaB) on memory in the neonatal iron overload model in rats. Rats received vehicle or 30.0-mg/kg Fe⁺² orally at postnatal days 12-14. When animals reached adulthood, they were given training in either novel object recognition or inhibitory avoidance. Histone acetylation in the dorsal hippocampus and the effects of NaB were examined in separate sets of rats. Iron overload led to a reduction in H3 lysine 9 acetylation in the hippocampus, without affecting the acetylation of other H3 and H4 lysine residues. A single systemic injection of NaB (1.2 g/kg) immediately after training ameliorated iron-induced memory impairments. The results suggest that a reduction in H3K9 acetylation might play a role in iron-induced memory impairment and support the view that HDACis can rescue memory dysfunction in models of brain disorders.
authors: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
authors: P F da
authors: PF
authors: Silva
authors: V A
authors: VA
authors: Garcia
authors: A da S
authors: Ada S
authors: Dornelles
authors: V K da
authors: VK
authors: Silva
authors: N
authors: N
authors: Maurmann
authors: B C D
authors: BC
authors: Portal
authors: R D P
authors: RD
authors: Ferreira
authors: F C
authors: FC
authors: Piazza
authors: R
authors: R
authors: Roesler
authors: N
authors: N
authors: Schröder
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002087:Butyrates / Q000627:therapeutic use*; D004195:Disease Models, Animal; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006657:Histones / Q000378:metabolism*; D007501:Iron / Q000009:adverse effects*; D008239:Lysine / Q000378:metabolism*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D018709:Statistics, Nonparametric
chemical_list: D002087:Butyrates; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D007501:Iron; D008239:Lysine