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Neuroscience ; 344: 360-370, 2017 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-28089578

RESUMO

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.


Assuntos
Hipocampo/enzimologia , Histona Desacetilases/metabolismo , Privação Materna , Transtornos da Memória/enzimologia , Reconhecimento Psicológico/fisiologia , Estresse Psicológico/enzimologia , Acetilação/efeitos dos fármacos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ácido Butírico/farmacologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Inibidores de Histona Desacetilases/farmacologia , Histonas/metabolismo , Masculino , Transtornos da Memória/tratamento farmacológico , Nootrópicos/farmacologia , Ratos Wistar , Reconhecimento Psicológico/efeitos dos fármacos
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