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Long-lasting recognition memory impairment and alterations in brain levels of cytokines and BDNF induced by maternal deprivation: effects of valproic acid and topiramate

  • Psychiatry and Preclinical Psychiatric Studies - Original Article
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Abstract

Exposure to stressful events early in life may have permanent deleterious consequences on nervous system function and increase the susceptibility to psychiatric conditions later in life. Maternal deprivation, commonly used as a source of neonatal stress, impairs memory in adult rats and reduces hippocampal brain-derived neurotrophic factor (BDNF) levels. Inflammatory cytokines, such as interleukins (IL) and tumor necrosis factor-α (TNF-α) have been shown to be increased in the peripheral blood of patients with psychiatric disorders. The aim of the present study was to investigate the effects of maternal separation on the levels of IL-10 and TNF-α, and BDNF in the hippocampus and prefrontal cortex of adult rats. We also evaluated the potential ameliorating properties of topiramate and valproic acid on memory deficits and cytokine and BDNF changes associated with maternal deprivation. The results indicated that, in addition to inducing memory deficits, maternal deprivation increased the levels of IL-10 in the hippocampus, and TNF-α in the hippocampus and in the cortex, and decreased hippocampal levels of BDNF, in adult life. Neither valproic acid nor topiramate were able to ameliorate memory deficits or the reduction in BDNF induced by maternal separation. The highest dose of topiramate was able to reduce IL-10 in the hippocampus and TNF-α in the prefrontal cortex, while valproate only reduced IL-10 levels in the hippocampus. These findings may have implications for a better understanding of the mechanisms associated with alterations observed in adult life induced by early stressful events, and for the proposal of novel therapeutic strategies.

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Acknowledgments

F.K. and N.S. are Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) Research fellows. Funding for this study was provided by Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazil (Procad 061/2007, grant AUX-PE 657/2008).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, Av. Ipiranga, 6681 Predio 12D, Porto Alegre, RS, 90619-900, Brazil

    Rose Mary Carvalho Pinheiro, Maria Noêmia Martins de Lima, Bernardo Chaves Dávila Portal, Stefano Boemler Busato, Lucio Falavigna, Rafael Dal Ponte Ferreira & Nadja Schröder

  2. National Institute for Translational Medicine (INCT-TM), Porto Alegre, RS, 90035-003, Brazil

    Maria Noêmia Martins de Lima, Bianca Wollenhaupt de Aguiar, Flávio Kapczinski & Nadja Schröder

  3. Bipolar Disorders Program and Laboratory of Molecular Psychiatry, Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil

    André Contri Paz, Bianca Wollenhaupt de Aguiar & Flávio Kapczinski

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  1. Rose Mary Carvalho Pinheiro
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Pinheiro, R.M.C., de Lima, M.N.M., Portal, B.C.D. et al. Long-lasting recognition memory impairment and alterations in brain levels of cytokines and BDNF induced by maternal deprivation: effects of valproic acid and topiramate. J Neural Transm 122, 709–719 (2015). https://doi.org/10.1007/s00702-014-1303-2

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