1. Long-lasting recognition memory impairment and alterations in brain levels of cytokines and BDNF induced by maternal deprivation: effects of valproic acid and topiramate.
- Author
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Pinheiro RM, de Lima MN, Portal BC, Busato SB, Falavigna L, Ferreira RD, Paz AC, de Aguiar BW, Kapczinski F, and Schröder N
- Subjects
- Animals, Exploratory Behavior drug effects, Exploratory Behavior physiology, Fructose analogs & derivatives, Fructose pharmacology, Hippocampus drug effects, Hippocampus growth & development, Male, Memory Disorders drug therapy, Memory Disorders etiology, Prefrontal Cortex drug effects, Prefrontal Cortex growth & development, Psychotropic Drugs pharmacology, Rats, Wistar, Recognition, Psychology drug effects, Recognition, Psychology physiology, Stress, Psychological drug therapy, Stress, Psychological etiology, Stress, Psychological metabolism, Topiramate, Valproic Acid pharmacology, Brain-Derived Neurotrophic Factor metabolism, Cytokines metabolism, Hippocampus metabolism, Maternal Deprivation, Memory Disorders metabolism, Prefrontal Cortex metabolism
- 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.
- Published
- 2015
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