gms | German Medical Science

64th Annual Meeting of the German Society of Neurosurgery (DGNC)

German Society of Neurosurgery (DGNC)

26 - 29 May 2013, Düsseldorf

Transplanted immature projection neurons maintain their molecular subtype identity and re-establish appropriate long distance connectivity within the postnatal mouse CNS

Meeting Abstract

  • Thomas V. Wuttke - MGH-HMS Ctr. Nervous Syst. Repair, Departments of Neurosurgery, Neurology, Neuroscience, Nayef Al-Rodhan Labs, Mass. General Hospital / Harvard Med. School, Boston, USA; Harvard Stem Cell Inst., Department of Stem Cell and Regenerative Biol, Harvard University, Cambridge, USA; Abteilung Neurochirurgie, Universitätsklinikum Tübingen, Deutschland; Abteilung Neurologie mit Schwerpunkt Epileptologie, Hertie-Institut für klinische Hirnforschung, Universität Tübingen, Deutschland
  • Foivos Markopoulos - Department of Molecular and Cellular Biology, Harvard University, Cambridge, USA; Center for Brain Science, Harvard University, Cambridge, USA
  • Aaron P. Wheeler - MGH-HMS Ctr. Nervous Syst. Repair, Departments of Neurosurgery, Neurology, Neuroscience, Nayef Al-Rodhan Labs, Mass. General Hospital / Harvard Med. School, Boston, USA; Harvard Stem Cell Inst., Department of Stem Cell and Regenerative Biol, Harvard University, Cambridge, USA
  • Venkatesh N. Murthy - Department of Molecular and Cellular Biology, Harvard University, Cambridge, USA; Center for Brain Science, Harvard University, Cambridge, USA
  • Jeffrey D. Macklis - MGH-HMS Ctr. Nervous Syst. Repair, Departments of Neurosurgery, Neurology, Neuroscience, Nayef Al-Rodhan Labs, Mass. General Hospital / Harvard Med. School, Boston, USA; Harvard Stem Cell Inst., Department of Stem Cell and Regenerative Biol, Harvard University, Cambridge, USA

Deutsche Gesellschaft für Neurochirurgie. 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Düsseldorf, 26.-29.05.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. DocP 077

doi: 10.3205/13dgnc494, urn:nbn:de:0183-13dgnc4943

Published: May 21, 2013

© 2013 Wuttke et al.
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Outline

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Objective: Most neurodegenerative and some acquired diseases of the central nervous system result in loss of specific subtypes of long distance projection neurons. For example, corticospinal motor neurons are centrally affected by traumatic spinal cord injury, and are the prototypical projection neurons, along with other developmentally closely related subcerebral projection neuron populations, that degenerate in ALS and related motor neuron diseases. Transplantation of developmentally appropriate immature neurons (including those potentially generated by directed in vitro differentiation of progenitors and/or embryonic stem cells or iPS cells) might enable repair of diseased neocortical circuitry. The success of such potential cellular replacement strategies will depend on the ability of newly incorporated neurons to maintain proper subtype identity and to re-establish functional and anatomically precise afferent dendritic and efferent axonal connectivity.

Method: We investigated the specificity and fidelity of connectivity established by transplanted immature projection neurons, employing a set of newly available reagents and markers of subtype-specific differentiation of neocortical projection neurons.

Results: Results reveal that transplanted GFP-positive embryonic immature subcerebral and callosal projection neurons develop and maintain correct molecular identity, and send long-distance axon projections to appropriate targets within the recipient brain and spinal cord. We are currently investigating the extent of functional integration of newly incorporated neurons within postnatal local and long distance projection circuitry using channelrhodopsin-2 assisted slice electrophysiology.

Conclusions: These results will also inform approaches toward potential generation and transplantation of donor neurons by directed differentiation of embryonic stem cells or iPS cells.