Abstract
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, p75NTR, 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.
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Funding
This research was supported by the National Council for Scientific and Technological Development (CNPq; Grant Numbers 308290/2015-1and 421643/2016-1 to NS); the National Institute for Translational Medicine (INCT-TM). M.R.B. is Research Career Awarded of the CNPq. V.C.D. is recipient of a PROBIC/FAPERGS fellowship. P. C. de F. C. and R.T.M. are recipients of BPA/PUCRS scholarships. L.W.K. is recipient of fellowship CAPES/PNPD Program.
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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted and approved by the Institutional Ethics Committee (SIPESQ# 7205).
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Alcalde, L.A., de Freitas, B.S., Machado, G.D.B. et al. Iron chelator deferiprone rescues memory deficits, hippocampal BDNF levels and antioxidant defenses in an experimental model of memory impairment. Biometals 31, 927–940 (2018). https://doi.org/10.1007/s10534-018-0135-1
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DOI: https://doi.org/10.1007/s10534-018-0135-1