title: Dual influences of early-life maternal deprivation on histone deacetylase activity and recognition memory in rats.
abstract: Exposure to stress early in life may negatively impact nervous system functioning, including increasing the proneness to learning and memory impairments later in life. Maternal deprivation, a model of early-life stress, hinders memory in adult rats and lessens brain-derived neurotrophic factor (BDNF) levels in the hippocampus in a very heterogeneous way among individuals. The main goal of the present study was to investigate the possible epigenetic modulation underlying recognition memory impairment and reduced BDNF levels in the hippocampus of adult maternally deprived rats. We also evaluated the potential ameliorating properties of the histone deacetylase (HDAC) inhibitor, sodium butyrate, on memory deficits and BDNF changes related to maternal deprivation. Maternally deprived animals were categorized as 'inferior learners' and 'superior learners' according to their performance in object recognition memory task in comparison to controls. Results indicated that HDAC activity was higher in individuals submitted to maternal deprivation with the worst cognitive performance (inferior learners). Acute administration of sodium butyrate increased histone H3 acetylation and BDNF levels, and restored recognition memory in maternally deprived animals with the worst cognitive performance. Moreover, we also showed that there is a positive correlation between BDNF levels and memory performance. Taken together, the results indicated that HDAC inhibitors could be considered as a possible therapeutic agent to improve cognitive performance in inferior learners. Further studies need to be conducted for a better comprehension of the mechanisms related to persistent alterations observed in adult life induced by early stressful circumstances and those leading to resilience.
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: Manoel Osório
authors.initials: MO
authors.lastname: Albuquerque Filho
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: Betânia Souza
authors.initials: BS
authors.lastname: de Freitas
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: Rebeca Carvalho Lacerda
authors.initials: RC
authors.lastname: Garcia
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: Pedro Castilhos de Freitas
authors.initials: PC
authors.lastname: Crivelaro
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: Nadja
authors.initials: N
authors.lastname: Schröder
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil. Electronic address: maria.lima@pucrs.br.
authors.forename: Maria Noêmia Martins
authors.initials: MN
authors.lastname: de Lima
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D020148:Butyric Acid / Q000494:pharmacology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008297:Male; D008426:Maternal Deprivation; D008569:Memory Disorders / Q000188:drug therapy / Q000201:enzymology*; D018697:Nootropic Agents / Q000494:pharmacology; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology*; D013315:Stress, Psychological / Q000201:enzymology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D018697:Nootropic Agents; D020148:Butyric Acid; D006655:Histone Deacetylases
keywords: BDNF; histone acetylation; object recognition; post-natal stress; sodium butyrate