Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90619-900, Brazil.
Laboratory of Genomics and Molecular Biology, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90619-900, Brazil.
Biometals. 2018 Dec;31(6):927-940. doi: 10.1007/s10534-018-0135-1. Epub 2018 Aug 16.
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, 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.
脑源性神经营养因子（BDNF）在神经发育和生理学以及病理状态中起着关键作用。尸检研究表明，BDNF 在受神经退行性疾病影响的患者的大脑中减少。铁积累也与神经退行性疾病的发病机制有关。在大鼠中，铁过载会导致持续的记忆缺陷，增加氧化应激和凋亡标志物，并降低突触标志物突触小体素的表达。地拉罗司（DFP）是一种口服铁螯合剂，用于治疗全身性铁过载疾病，最近已用于帕金森病的测试。在这里，我们研究了铁过载对 BDNF 水平以及编码 TrkB、p75、过氧化氢酶 (CAT) 和 NQO1 的基因的 mRNA 表达的影响。我们还旨在研究 DFP 对铁诱导损伤的影响。大鼠在出生后第 12-14 天接受铁或载体，并在成年时接受慢性 DFP 或水（载体）。在螯合治疗开始后 19 天测试识别记忆。在 DFP 治疗的最后一天 24 小时后，在海马体中进行 BDNF 测量和基因表达分析。DFP 恢复了记忆并增加了海马体中的 BDNF 水平，改善了铁诱导的影响。在新生儿期铁过载减少，而 DFP 治疗能够挽救抗氧化酶 CAT 和 NQO1 的表达。
