title: Long-lasting recognition memory impairment and alterations in brain levels of cytokines and BDNF induced by maternal deprivation: effects of valproic acid and topiramate.
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.
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, Av. Ipiranga, 6681 Predio 12D, Porto Alegre, RS, 90619-900, Brazil.
authors.forename: Rose Mary Carvalho
authors.initials: RM
authors.lastname: Pinheiro
authors.forename: Maria Noêmia Martins
authors.initials: MN
authors.lastname: de Lima
authors.forename: Bernardo Chaves Dávila
authors.initials: BC
authors.lastname: Portal
authors.forename: Stefano Boemler
authors.initials: SB
authors.lastname: Busato
authors.forename: Lucio
authors.initials: L
authors.lastname: Falavigna
authors.forename: Rafael Dal Ponte
authors.initials: RD
authors.lastname: Ferreira
authors.forename: André Contri
authors.initials: AC
authors.lastname: Paz
authors.forename: Bianca Wollenhaupt
authors.initials: BW
authors.lastname: de Aguiar
authors.forename: Flávio
authors.initials: F
authors.lastname: Kapczinski
authors.forename: Nadja
authors.initials: N
authors.lastname: Schröder
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005632:Fructose / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D008426:Maternal Deprivation; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D011619:Psychotropic Drugs / Q000494:pharmacology; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D013315:Stress, Psychological / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D000077236:Topiramate; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D011619:Psychotropic Drugs; D000077236:Topiramate; D005632:Fructose; D014635:Valproic Acid