PMID- 30117045 OWN - NLM STAT- MEDLINE DCOM- 20190903 LR - 20190903 IS - 1572-8773 (Electronic) IS - 0966-0844 (Linking) VI - 31 IP - 6 DP - 2018 Dec TI - Iron chelator deferiprone rescues memory deficits, hippocampal BDNF levels and antioxidant defenses in an experimental model of memory impairment. PG - 927-940 LID - 10.1007/s10534-018-0135-1 [doi] AB - Brain-derived neurotrophic factor (BDNF) plays a key role in neural development and physiology, as well as in pathological states. Post-mortem studies demonstrate that BDNF is reduced in the brains of patients affected by neurodegenerative diseases. Iron accumulation has also been associated to the pathogenesis of neurodegenerative diseases. In rats, iron overload induces persistent memory deficits, increases oxidative stress and apoptotic markers, and decreases the expression of the synaptic marker, synaptophysin. Deferiprone (DFP) is an oral iron chelator used for the treatment of systemic iron overload disorders, and has recently been tested for Parkinson's disease. Here, we investigated the effects of iron overload on BDNF levels and on mRNA expression of genes encoding TrkB, p75(NTR), catalase (CAT) and NQO1. We also aimed at investigating the effects of DFP on iron-induced impairments. Rats received iron or vehicle at postnatal days 12-14 and when adults, received chronic DFP or water (vehicle). Recognition memory was tested 19 days after the beginning of chelation therapy. BDNF measurements and expression analyses in the hippocampus were performed 24 h after the last day of DFP treatment. DFP restored memory and increased hippocampal BDNF levels, ameliorating iron-induced effects. Iron overload in the neonatal period reduced, while treatment with DFP was able to rescue, the expression of antioxidant enzymes CAT and NQO1. FAU - Alcalde, Luisa Azambuja AU - Alcalde LA AD - Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90619-900, Brazil. FAU - de Freitas, Betania Souza AU - de Freitas BS AD - Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90619-900, Brazil. FAU - Machado, Gustavo Dalto Barroso AU - Machado GDB AD - Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90619-900, Brazil. FAU - de Freitas Crivelaro, Pedro Castilhos AU - de Freitas Crivelaro PC AD - Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90619-900, Brazil. FAU - Dornelles, Victoria Campos AU - Dornelles VC AD - Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90619-900, Brazil. FAU - Gus, Henrique AU - Gus H AD - Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90619-900, Brazil. FAU - Monteiro, Ricardo Tavares AU - Monteiro RT AD - Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90619-900, Brazil. FAU - Kist, Luiza Wilges AU - Kist LW AD - Laboratory of Genomics and Molecular Biology, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90619-900, Brazil. AD - Graduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90610-000, Brazil. FAU - Bogo, Mauricio Reis AU - Bogo MR AD - Laboratory of Genomics and Molecular Biology, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90619-900, Brazil. AD - Graduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90610-000, Brazil. FAU - Schroder, Nadja AU - Schroder N AUID- ORCID: 0000-0002-4227-5702 AD - Departamento de Fisiologia, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Porto Alegre, RS, 90050-170, Brazil. nadja_s@terra.com.br. AD - National Institute of Science and Technology for Translational Medicine (INCT-TM), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brasilia, 71605-001, Brazil. nadja_s@terra.com.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180816 PL - Netherlands TA - Biometals JT - Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine JID - 9208478 RN - 0 (Antioxidants) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Iron Chelating Agents) RN - 2BTY8KH53L (Deferiprone) SB - IM MH - Animals MH - Antioxidants/chemistry/*pharmacology MH - Brain-Derived Neurotrophic Factor/analysis/*metabolism MH - Deferiprone/chemistry/*pharmacology MH - *Disease Models, Animal MH - Female MH - Hippocampus/drug effects MH - Iron Chelating Agents/chemistry/*pharmacology MH - Memory Disorders/*drug therapy MH - Oxidative Stress/*drug effects MH - Rats MH - Rats, Wistar OTO - NOTNLM OT - BDNF OT - Catalase OT - Deferiprone OT - Iron OT - Memory OT - Neurodegeneration EDAT- 2018/08/18 06:00 MHDA- 2019/09/04 06:00 CRDT- 2018/08/18 06:00 PHST- 2018/07/09 00:00 [received] PHST- 2018/08/12 00:00 [accepted] PHST- 2018/08/18 06:00 [pubmed] PHST- 2019/09/04 06:00 [medline] PHST- 2018/08/18 06:00 [entrez] AID - 10.1007/s10534-018-0135-1 [pii] AID - 10.1007/s10534-018-0135-1 [doi] PST - ppublish SO - Biometals. 2018 Dec;31(6):927-940. doi: 10.1007/s10534-018-0135-1. Epub 2018 Aug 16.