Memory impairment induced by brain iron overload is accompanied by reduced H3K9 acetylation and ameliorated by sodium butyrate

• Published in: Neuroscience Vol. 200; pp. 42 - 49
• Main Authors: da Silva, P.F, Garcia, V.A, Dornelles, A. da S, da Silva, V.K, Maurmann, N, Portal, B.C.D, Ferreira, R.D.P, Piazza, F.C, Roesler, R, Schröder, N
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 03-01-2012; Elsevier
• Subjects: Acetylation - drug effects; Analysis of Variance; Animals; Animals, Newborn; Avoidance Learning - drug effects; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Butyrates - therapeutic use; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; histone acetylation; Histone Deacetylase Inhibitors - therapeutic use; Histones - metabolism; inhibitory avoidance; iron; Iron - adverse effects; Lysine - metabolism; Memory Disorders - chemically induced; Memory Disorders - drug therapy; Memory Disorders - pathology; neurodegeneration; Neurology; object recognition; Rats; Rats, Wistar; Recognition (Psychology) - drug effects; sodium butyrate; Statistics, Nonparametric; Vertebrates: nervous system and sense organs; object recognition; sodium butyrate; HDACs; OR; LTM; inhibitory avoidance; neurodegeneration; long-term memory; NaB; HDAC inhibitor; IA; iron; histone deacetylases; HDACi; histone acetylation; Memory; Central nervous system; Iron; Encephalon; Sodium; Degeneration; Acetylation; Histone; Avoidance
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2011.10.038

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.