title: Sulforaphane rescues memory dysfunction and synaptic and mitochondrial alterations induced by brain iron accumulation.
abstract: Iron overload contributes to the development of neurodegeneration and the exacerbation of normal apoptosis rates, largely due to its participation in the Fenton reaction and production of reactive oxygen species (ROS). Mitochondria constitute the major intracellular source of ROS and the main target of attack by free radicals. They are dynamic organelles that bind (fusion) and divide (fission) in response to environmental stimuli, developmental status, and energy needs of the cells. Sulforaphane (SFN) is a natural compound that displays antioxidant and anti-inflammatory activities. This study aims to investigate the effects of SFN on memory deficits and changes in markers of mitochondrial function, DNM1L and OPA1, and the synaptic marker, synaptophysin, induced by neonatal iron treatment. Male rats received vehicle or carbonyl iron (30mg/kg) from the 12th to the 14th postnatal day. In adulthood, they were treated with saline or SFN (0.5 or 5mg/kg) for 14days every other day. Memory deficits were assessed using the object recognition task. DNM1L, OPA1, and synaptophysin levels in the hippocampus were quantified by Western blotting. Results showed that SFN was able to reverse iron-induced decreases in mitochondrial fission protein, DNM1L, as well as synaptophysin levels in the hippocampus, leading to a recovery of recognition memory impairment induced by iron. These findings suggest that SFN may be further investigated as potential agent for the treatment of cognitive deficits associated with neurodegenerative disorders.
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: I C
authors.initials: IC
authors.lastname: Lavich
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: B S
authors.initials: BS
authors.lastname: de Freitas
authors.affiliation: Laboratório de Biologia Genômica e Molecular, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Medicina e Ciências da Saúde, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: L W
authors.initials: LW
authors.lastname: Kist
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Falavigna
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: V A
authors.initials: VA
authors.lastname: Dargél
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: L M
authors.initials: LM
authors.lastname: Köbe
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Aguzzoli
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: B
authors.initials: B
authors.lastname: Piffero
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: P Z
authors.initials: PZ
authors.lastname: Florian
authors.affiliation: Laboratório de Biologia Genômica e Molecular, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Medicina e Ciências da Saúde, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil; National Institute for Translational Medicine (INCT-TM), 90035-003 Porto Alegre, RS, Brazil.
authors.forename: M R
authors.initials: MR
authors.lastname: Bogo
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil; National Institute for Translational Medicine (INCT-TM), 90035-003 Porto Alegre, RS, Brazil.
authors.forename: M N M
authors.initials: MN
authors.lastname: de Lima
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil; National Institute for Translational Medicine (INCT-TM), 90035-003 Porto Alegre, RS, Brazil. Electronic address: nadja.schroder@pucrs.br.
authors.forename: N
authors.initials: N
authors.lastname: Schröder
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D058085:Iron Compounds / Q000378:metabolism* / Q000633:toxicity; D017879:Isothiocyanates / Q000627:therapeutic use*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D013454:Sulfoxides; D013569:Synapses / Q000378:metabolism*
chemical_list: D016588:Anticarcinogenic Agents; D058085:Iron Compounds; D017879:Isothiocyanates; D013454:Sulfoxides; C515100:iron pentacarbonyl; D007501:Iron; D002374:Catalase; D005979:Glutathione Peroxidase; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D020558:GTP Phosphohydrolases; C498811:Opa1 protein, rat; C519851:Dnm1l protein, rat; D034281:Dynamins; C016766:sulforaphane
keywords: iron; mitochondria; neurodegenerative disorders; recognition memory; sulforaphane; synapse