PMID- 25182413 OWN - NLM STAT- MEDLINE DCOM- 20160113 LR - 20211021 IS - 1435-1463 (Electronic) IS - 0300-9564 (Linking) VI - 122 IP - 5 DP - 2015 May TI - Long-lasting recognition memory impairment and alterations in brain levels of cytokines and BDNF induced by maternal deprivation: effects of valproic acid and topiramate. PG - 709-19 LID - 10.1007/s00702-014-1303-2 [doi] AB - 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-alpha (TNF-alpha) 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-alpha, 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-alpha 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-alpha 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. FAU - Pinheiro, Rose Mary Carvalho AU - Pinheiro RM AD - Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, Av. Ipiranga, 6681 Predio 12D, Porto Alegre, RS, 90619-900, Brazil. FAU - de Lima, Maria Noemia Martins AU - de Lima MN FAU - Portal, Bernardo Chaves Davila AU - Portal BC FAU - Busato, Stefano Boemler AU - Busato SB FAU - Falavigna, Lucio AU - Falavigna L FAU - Ferreira, Rafael Dal Ponte AU - Ferreira RD FAU - Paz, Andre Contri AU - Paz AC FAU - de Aguiar, Bianca Wollenhaupt AU - de Aguiar BW FAU - Kapczinski, Flavio AU - Kapczinski F FAU - Schroder, Nadja AU - Schroder N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140903 PL - Austria TA - J Neural Transm (Vienna) JT - Journal of neural transmission (Vienna, Austria : 1996) JID - 9702341 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cytokines) RN - 0 (Psychotropic Drugs) RN - 0H73WJJ391 (Topiramate) RN - 30237-26-4 (Fructose) RN - 614OI1Z5WI (Valproic Acid) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cytokines/*metabolism MH - Exploratory Behavior/drug effects/physiology MH - Fructose/analogs & derivatives/pharmacology MH - Hippocampus/drug effects/growth & development/*metabolism MH - Male MH - *Maternal Deprivation MH - Memory Disorders/drug therapy/etiology/*metabolism MH - Prefrontal Cortex/drug effects/growth & development/*metabolism MH - Psychotropic Drugs/pharmacology MH - Rats, Wistar MH - Recognition, Psychology/drug effects/physiology MH - Stress, Psychological/drug therapy/etiology/metabolism MH - Topiramate MH - Valproic Acid/pharmacology EDAT- 2014/09/04 06:00 MHDA- 2016/01/14 06:00 CRDT- 2014/09/04 06:00 PHST- 2014/04/17 00:00 [received] PHST- 2014/08/22 00:00 [accepted] PHST- 2014/09/04 06:00 [entrez] PHST- 2014/09/04 06:00 [pubmed] PHST- 2016/01/14 06:00 [medline] AID - 10.1007/s00702-014-1303-2 [doi] PST - ppublish SO - J Neural Transm (Vienna). 2015 May;122(5):709-19. doi: 10.1007/s00702-014-1303-2. Epub 2014 Sep 3.