Professor Yves Barde
FRS
Professor / Sêr Cymru Research Chair in Neurobiology
- bardey@cardiff.ac.uk
- +44 (0)29 2087 0987
- Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX
- Media commentator
Overview
Our work focuses on growth factors known to play key roles in brain development and function. Some of these growth factors are found not only in the brain, but also in circulating blood platelets and we are exploring the possibility that they may be delivered to the nervous system by small vesicles derived from platelets. To this end we have generated a new mouse model allowing this hypothesis to be tested. This approach takes advantage of a major difference between mouse and primates with regard to the growth factor content of platelets. This work could lead to novel ways of delivering genetically encoded macromolecules to the brain over long periods of time.
Biography
Medical School & Doctor of Medicine (Geneva, 1975)
Swiss Certificate of Molecular Biology (Basel, 1977)
Postdoctoral fellow, Department of Pharmacology (Basel, 1976)
Postdoctoral fellow, Max-Planck Institute of Psychiatry (Martinsried, Germany, 1979)
Schilling Professorship, Max-Planck Institute of Psychiatry (Martinsried, Germany, 1989)
Scientific member of the Max-Planck Society, Director, Max-Planck Institute of Neurobiology (Martinsried, Germany, 1991)
Honorary Professor of Neurobiology, Ludwig Maximilian University (Munich, Germany, 1993)
Director of the Friedrich Miescher Institute for Biomedical Research (Basel, 2001)
Professor of Neurobiology Phil II Faculty (Basel, 2001)
External Scientific Member of the Max-Planck Institute of Neurobiology (Martinsried, 2002)
Professor of Neurobiology, Division of Pharmacology and Neurobiology (Basel, 2003).
Sêr Cymru Research Chair in Neurobiology (Cardiff University, 2013)
Fellow of the Royal Society (London, 2017)
Publications
2020
- Naegelin, Y.et al. 2020. Levels of brain-derived neurotrophic factor in patients with multiple sclerosis. Annals of Clinical and Translational Neurology (10.1002/acn3.51215)
- Wosnitzka, E.et al. 2020. A new mouse line reporting the translation of brain-derived neurotrophic factor using green fluorescent protein. eNeuro 7(1), article number: ENEURO.0462-19.2019. (10.1523/ENEURO.0462-19.2019)
2018
- Merkouris, S.et al. 2018. Fully human agonist antibodies to TrkB using autocrine cell-based selection from a combinatorial antibody library. Proceedings of the National Academy of Sciences 115(30), pp. E7023-E7032. (10.1073/pnas.1806660115)
- Naegelin, Y.et al. 2018. Measuring and validating the levels of brain-derived neurotrophic factor in human serum. eNeuro 5(2), article number: e0419-17.2018. (10.1523/ENEURO.0419-17.2018)
2017
- Barde, Y. and Cassels, L. 2017. Scaling pain threshold with microRNAs. Science 356(6343), pp. 1124-1125. (10.1126/science.aan6784)
2016
- Binley, K. E.et al. 2016. Brain-derived neurotrophic factor prevents dendritic retraction of adult mouse retinal ganglion cells. European Journal of Neuroscience 44(3), pp. 2028-2039. (10.1111/ejn.13295)
- Chacon-Fernandez, P.et al. 2016. Brain-derived neurotrophic factor in megakaryocytes. Journal of Biological Chemistry 291(19), pp. 9872-9881. (10.1074/jbc.M116.720029)
2015
- Sirko, S.et al. 2015. Astrocyte reactivity after brain injury-: The role of galectins 1 and 3. Glia 63(12), pp. 2340-2361. (10.1002/glia.22898)
2013
- Dekkers, M. p. J., Nikoletopoulou, V. and Barde, Y. 2013. Death of developing neurons: New insights and implications for connectivity. Journal of Cell Biology 203(3), pp. 385-393. (10.1083/jcb.201306136)
- Dekkers, M. P. J. and Barde, Y. 2013. Programmed cell death in neuronal development. Science 340(6128), pp. 39-41. (10.1126/science.1236152)
2012
- Yazdani, M.et al. 2012. Disease modeling using embryonic stem cells: MeCP2 regulates nuclear size and RNA synthesis in neurons. Stem Cells 30(10), pp. 2128-2139. (10.1002/stem.1180)
- Deogracias, R.et al. 2012. Fingolimod, a sphingosine-1 phosphate receptor modulator, increases BDNF levels and improves symptoms of a mouse model of Rett syndrome. Proceedings of the National Academy of Sciences of the United States of America 109(35), pp. 14230-14235. (10.1073/pnas.1206093109)
- Tiwari, V. K.et al. 2012. Target genes of Topoisomerase IIβ regulate neuronal survival and are defined by their chromatin state. Proceedings of the National Academy of Sciences of the United States of America 109(16), pp. E934-E943. (10.1073/pnas.1119798109)
- Dieni, S.et al. 2012. BDNF and its pro-peptide are stored in presynaptic dense core vesicles in brain neurons. Journal of Cell Biology 196(6), pp. 775-788. (10.1083/jcb.201201038)
- Bischoff, V.et al. 2012. Seizure-induced neuronal death is suppressed in the absence of the endogenous lectin galectin-1. Journal of Neuroscience 32(44), pp. 15590-15600. (10.1523/JNEUROSCI.4983-11.2012)
2011
- Bischoff, V., Nikoletopoulou, V. and Barde, Y. 2011. Sauver ou tuer. Médecine Sciences M/S 27(2), pp. 119-121. (10.1051/medsci/2011272119)
2010
- Nikoletopoulou, V.et al. 2010. Neurotrophin receptors TrkA and TrkC cause neuronal death whereas TrkB does not. Nature 467(7311), pp. 59-63. (10.1038/nature09336)
- Rauskolb, S.et al. 2010. Global deprivation of brain-derived neurotrophic factor in the CNS reveals an area-specific requirement for dendritic growth. Journal of Neuroscience 30(5), pp. 1739-1749. (10.1523/JNEUROSCI.5100-09.2010)
2009
- Pasutto, F.et al. 2009. Heterozygous NTF4 mutations impairing neurotrophin-4 signaling in patients with primary open-angle glaucoma. American Journal of Human Genetics 85(4), pp. 447-456. (10.1016/j.ajhg.2009.08.016)
- Barde, Y. 2009. Caution urged in trial of stem cells to treat spinal-cord injury [Letter]. Nature 458(7234), pp. 29-29. (10.1038/458029a)
2008
- Schrenk-Siemens, K.et al. 2008. Embryonic stem cell-derived neurons as a cellular system to study gene function: lack of amyloid precursor proteins APP and APLP2 leads to defective synaptic transmission. Stem Cells 26(8), pp. 2153-2163. (10.1634/stemcells.2008-0010)
- Matsumoto, T.et al. 2008. Biosynthesis and processing of endogenous BDNF: CNS neurons store and secrete BDNF, not pro-BDNF. Nature Neuroscience 11(2), pp. 131-133. (10.1038/nn2038)
2007
- Nicholson, J. R.et al. 2007. Melanocortin-4 receptor activation stimulates hypothalamic brain-derived neurotrophic factor release to regulate food intake, body temperature and cardiovascular function. Journal of Neuroendocrinology 19(12), pp. 974-982. (10.1111/j.1365-2826.2007.01610.x)
- Affolter, M. and Barde, Y. 2007. Self-renewal in the fly kidney. Developmental Cell 13(3), pp. 321-322. (10.1016/j.devcel.2007.08.002)
- Plachta, N.et al. 2007. Identification of a lectin causing the degeneration of neuronal processes using engineered embryonic stem cells. Nature Neuroscience 10(6), pp. 712-719. (10.1038/nn1897)
- Bibel, M.et al. 2007. Generation of a defined and uniform population of CNS progenitors and neurons from mouse embryonic stem cells. Nature Protocols 2(5), pp. 1034-1043. (10.1038/nprot.2007.147)
2005
- Zagrebelsky, M.et al. 2005. The p75 neurotrophin receptor negatively modulates dendrite complexity and spine density in hippocampal neurons. Journal of Neuroscience 25(43), pp. 9989-9999. (10.1523/JNEUROSCI.2492-05.2005)
- Rosch, H.et al. 2005. The neurotrophin receptor p75NTR modulates long-term depression and regulates the expression of AMPA receptor subunits in the hippocampus. Proceedings of the National Academy of Sciences of the United States of America 102(20), pp. 7362-7367. (10.1073/pnas.0502460102)
- Götz, M. and Barde, Y. 2005. Radial glial cells: defined and major intermediates between embryonic stem cells and CNS neurons. Neuron 46(3), pp. 369-372. (10.1016/j.neuron.2005.04.012)
2004
- Plachta, N.et al. 2004. Developmental potential of defined neural progenitors derived from mouse embryonic stem cells. Development 131(21), pp. 5449-5456. (10.1242/dev.01420)
- Bibel, M.et al. 2004. Differentiation of mouse embryonic stem cells into a defined neuronal lineage. Nature Neuroscience 7(9), pp. 1003-1009. (10.1038/nn1301)
- Barde, Y. 2004. Death of injured neurons caused by the precursor of nerve growth factor. Proceedings of the National Academy of Sciences of the United States of America 101(16), pp. 5703-5704. (10.1073/pnas.0401374101)
2003
- Andorfer, C.et al. 2003. Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms. Journal of Neurochemistry 86(3), pp. 582-590. (10.1046/j.1471-4159.2003.01879.x)
2002
- Barde, Y. 2002. Neurobiology: Neurotrophin channels excitement. Nature 419(6908), pp. 683-684. (10.1038/419683a)
- Wernig, M.et al. 2002. Tau EGFP embryonic stem cells: an efficient tool for neuronal lineage selection and transplantation. Journal of Neuroscience Research 69(6), pp. 918-924. (10.1002/jnr.10395)
- Heins, N.et al. 2002. Glial cells generate neurons: the role of the transcription factor Pax6. Nature Neuroscience 5(4), pp. 308-315. (10.1038/nn828)
- Dechant, G. and Barde, Y. 2002. The neurotrophin receptor p75NTR: novel functions and implications for diseases of the nervous system. Nature Neuroscience 5(11), pp. 1131-1136. (10.1038/nn1102-1131)
2001
- Benzel, I., Barde, Y. and Casademunt, E. 2001. Strain-specific complementation between NRIF1 and NRIF2, two zinc finger proteins sharing structural and biochemical properties. Gene 281(1-2), pp. 19-30. (10.1016/S0378-1119(01)00730-2)
Much has been learned about molecular mechanisms operating in the mammalian nervous system using genetically modified animals. In particular, the relevance of growth factors initially identified on the basis of cell culture assays could be firmly established by selectively eliminating the corresponding genes, typically using the mouse as model organism. These experiments have greatly helped understanding the physiology of brain-derived neurotrophic factor (BDNF) and of its tyrosine kinase receptor TrkB. BDNF is a secreted protein initially identified on the basis of its ability to promote the survival of specific populations of sensory neurons (https://www.embopress.org/doi/abs/10.1002/j.1460-2075.1982.tb01207.x). Most of the current work now focusses on the role of BDNF in synaptic plasticity, a key aspect of memory-related mechanisms, as well as in neuroprotection in humans. Whilst the generation of mouse mutants has been a key driver thus far, it is also evident that there are major differences between primates and rodents. These include the distribution of BDNF and the sites of its biosynthesis. In particular, circulating blood platelets contain significant levels of BDNF in humans, higher than in the brain (https://www.eneuro.org/content/5/2/ENEURO.0419-17.2018). But such is not the case in the mouse, with the implication that the hypothesis that blood-derived BDNF may impact brain function could not be tested thus far. This is as such an interesting question given that the levels of BDNF increase in human serum after physical exercise and that the benefits of exercise towards maintaining or improving important aspects of brain function are well appreciated.
Our recent work led to the identification of megakaryocytes as the cellular origin of BDNF in human platelets (http://www.jbc.org/content/291/19/9872). Based on the related observation that mouse megakaryocytes do not contain BDNF, we recently generated a mouse model mimicking the situation in primates. In collaboration with colleagues at Cardiff University we are testing the possible benefits of blood-derived BDNF using this mouse model.
Work in our laboratory also involves the extensive use of neurons derived from embryonic stem cells to test novel reagents activating the BDNF receptor TrkB. This work involves collaborations with the biotechnology industry giving us access to novel antibodies able to activate TrkB and other receptors of interest (see https://www.pnas.org/content/115/30/E7023).