Dysregulation of BDNF-TrkB signaling in developing hippocampal neurons by Pb(2+): implications for an environmental basis of neurodevelopmental disorders.

Toxicological Sciences : an Official Journal of the Society of Toxicology
Kirstie H StansfieldTomás R Guilarte

Abstract

Dysregulation of synaptic development and function has been implicated in the pathophysiology of neurodegenerative disorders and mental disease. A neurotrophin that has an important function in neuronal and synaptic development is brain-derived neurotrophic factor (BDNF). In this communication, we examined the effects of lead (Pb(2+)) exposure on BDNF-tropomyosin-related kinase B (TrkB) signaling during the period of synaptogenesis in cultured neurons derived from embryonic rat hippocampi. We show that Pb(2+) exposure decreases BDNF gene and protein expression, and it may also alter the transport of BDNF vesicles to sites of release by altering Huntingtin phosphorylation and protein levels. Combined, these effects of Pb(2+) resulted in decreased concentrations of extracellular mature BDNF. The effect of Pb(2+) on BDNF gene expression was associated with a specific decrease in calcium-sensitive exon IV transcript levels and reduced phosphorylation and protein expression of the transcriptional repressor methyl-CpG-binding protein (MeCP2). TrkB protein levels and autophosphorylation at tyrosine 816 were significantly decreased by Pb(2+) exposure with a concomitant increase in p75 neurotrophin receptor (p75(NTR)) levels and altered...Continue Reading

References

May 13, 1977·Brain Research·G A Banker, W M Cowan
Oct 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·M MetsisH Persson
Mar 8, 1996·The Journal of Biological Chemistry·M Canossa ShooterEM
Apr 16, 1996·Proceedings of the National Academy of Sciences of the United States of America·J N JovanovicA J Czernik
Feb 1, 1997·Neuron·B D Carter, G R Lewin
Feb 11, 1998·Physiological Reviews·R M Fitzsimonds, M M Poo
Mar 30, 1999·Brain Research. Molecular Brain Research·M K Nihei, T R Guilarte
Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·M E AndrésG Mandel
Mar 22, 2000·Nature Neuroscience·J N JovanovicT S Sihra
Dec 1, 2001·Science·R LeeB L Hempstead
Dec 14, 2001·The Journal of Biological Chemistry·Tadahiro NumakawaHiroshi Hatanaka
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
May 10, 2002·Environmental Science & Technology·Joel Tickner
Oct 9, 2002·Neuron·Liliana MinichielloMartin Korte
Dec 14, 2002·Brain Research. Developmental Brain Research·Christopher D ToscanoTomás R Guilarte
Apr 5, 2003·Annual Review of Biochemistry·Eric J Huang, Louis F Reichardt
Apr 18, 2003·The New England Journal of Medicine·Richard L CanfieldBruce P Lanphear
Jun 6, 2003·Progress in Neurobiology·Volkmar LessmannMarzia Malcangio
Nov 8, 2003·Brain Research. Developmental Brain Research·Christopher D ToscanoTomás R Guilarte
Apr 6, 2004·Environmental Health Perspectives·Mark G A OplerEzra S Susser
Jun 26, 2004·Annual Review of Neuroscience·Thomas C Sudhof

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Citations

Sep 4, 2013·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Ning LiWenJie Li
Dec 19, 2012·Epigenomics·Marie-Claude SenutDouglas Ruden
Jun 23, 2015·Risk Analysis : an Official Publication of the Society for Risk Analysis·Katherine von StackelbergBirgit Claus Henn
Nov 3, 2016·BMC Pharmacology & Toxicology·Sara Rose GuarigliaTomas R Guilarte
Dec 17, 2016·Epigenomics·Sarah S ParkCathrine Hoyo
Jan 26, 2017·Environmental Toxicology and Chemistry·Hongwei TuFei Zou
Oct 11, 2017·International Journal of Environmental Research and Public Health·David A GeierMark R Geier
Jan 5, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yulan WuHui-Li Wang
Dec 8, 2017·Critical Reviews in Clinical Laboratory Sciences·Prasenjit MitraPraveen Sharma
Dec 19, 2012·Epilepsia·Pablo M Casillas-EspinosaTerence J O'Brien
Mar 1, 2013·Toxicology Research·April P Neal, Tomas R Guilarte
May 8, 2018·Experimental and Therapeutic Medicine·Zhijun LuYujia Wang
Apr 18, 2018·Frontiers in Genetics·Garima SinghJay S Schneider
Apr 27, 2018·Biological Trace Element Research·Sung Min NamJong-Hwan Lee
Feb 26, 2020·Environmental Health : a Global Access Science Source·Francesca PistollatoAnna Bal-Price
Aug 4, 2020·Molecular Neurobiology·Meredith K LothTomás R Guilarte
Oct 14, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Xiao-Lei ZhangTomás R Guilarte
Sep 4, 2020·Neurotoxicology·Omamuyovwi M IjomoneMichael Aschner

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