title: Total and mitochondrial nitrosative stress, decreased brain-derived neurotrophic factor (BDNF) levels and glutamate uptake, and evidence of endoplasmic reticulum stress in the hippocampus of vitamin A-treated rats.
abstract: Vitamin A supplementation has caused concern among public health researchers due to its ability in decreasing life quality from acute toxicological effects to increasing mortality rates among vitamin supplement users. For example, it was described cognitive decline (i.e. irritability, anxiety, and depression) in patients subjected to long-term vitamin A therapy, as occurs in cancer treatment. However, the mechanism by which vitamin A affects mammalian cognition is not completely understood. Then, we performed the present work to investigate the effects of vitamin A supplementation at clinical doses (1,000-9,000 IU/kg day(-1)) for 28 days on rat hippocampal nitrosative stress levels (both total and mitochondrial), bioenergetics states, brain-derived neurotrophic factor (BDNF), alpha- and beta-synucleins, BiP and dopamine receptor 2 (D2 receptor) contents, and glutamate uptake. We observed mitochondrial impairment regarding respiratory chain function: increased complex I-III, but decreased complex IV enzyme activity. Also, decreased BDNF levels were observed in vitamin A-treated rats. The present data demonstrates, at least in part, that mitochondrial dysfunction and decreased BDNF and D2 receptors levels, as well as decreased glutamate uptake may take an important role in the mechanism behind the previously reported cognitive disturbances associated to vitamin A supplementation.
authors.affiliation: Centro de Estudos em Estresse Oxidativo (Lab. 32), Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Av. Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, CEP 90035-003, Brazil. mrobioq@yahoo.com.br
authors.forename: Marcos Roberto
authors.initials: MR
authors.lastname: de Oliveira
authors.forename: Ricardo Fagundes
authors.initials: RF
authors.lastname: da Rocha
authors.forename: Laura
authors.initials: L
authors.lastname: Stertz
authors.forename: Gabriel Rodrigo
authors.initials: GR
authors.lastname: Fries
authors.forename: Diogo Losch
authors.initials: DL
authors.lastname: de Oliveira
authors.forename: Flávio
authors.initials: F
authors.lastname: Kapczinski
authors.forename: José Cláudio Fonseca
authors.initials: JC
authors.lastname: Moreira
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D019587:Dietary Supplements; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D013312:Stress, Physiological; D014801:Vitamin A / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology; D051844:alpha-Synuclein / Q000378:metabolism; D051846:beta-Synuclein / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C539791:Bax-inhibiting peptide, BIP; D019208:Brain-Derived Neurotrophic Factor; D009842:Oligopeptides; D010446:Peptide Fragments; D026361:Reactive Nitrogen Species; D000067759:Receptor for Advanced Glycation End Products; D017448:Receptors, Dopamine D2; D011971:Receptors, Immunologic; D014815:Vitamins; D051844:alpha-Synuclein; C078592:amyloid beta-protein (1-40); D051846:beta-Synuclein; D014801:Vitamin A; D018698:Glutamic Acid