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Neural transplantation: restoring complex circuitry in the striatum

Fricker-Gates, Rosemary A.; Lundberg, Cecilia LU and Dunnett, Stephen B. (2001) In Restorative Neurology and Neuroscience 19(1-2). p.119-138
Abstract
During the last 30 years, the promise of neural transplantation as a therapeutic strategy for neurodegenerative disease has been slowly recognised. Across the world, clinical transplants of embryonic primary dopamine neurones have been shown to ameliorate some of the motor deficits in Parkinson s disease (PD) patients, and more recently, systematic clinical trials have been initiated for the replacement of striatal projection neurones lost in Huntington's disease (HD). Clinical transplantation as a prospective therapy for HD poses a particular set of difficulties. The hallmarks of this neurodegenerative disease include extensive loss of medium spiny long-distance projection neurones of the caudate and putamen, affecting downstream target... (More)
During the last 30 years, the promise of neural transplantation as a therapeutic strategy for neurodegenerative disease has been slowly recognised. Across the world, clinical transplants of embryonic primary dopamine neurones have been shown to ameliorate some of the motor deficits in Parkinson s disease (PD) patients, and more recently, systematic clinical trials have been initiated for the replacement of striatal projection neurones lost in Huntington's disease (HD). Clinical transplantation as a prospective therapy for HD poses a particular set of difficulties. The hallmarks of this neurodegenerative disease include extensive loss of medium spiny long-distance projection neurones of the caudate and putamen, affecting downstream target nuclei, the globus pallidus and substantia nigra, leading to dysregulation of motor control. In addition, extensive loss of cortical neurones that form the afferent systems to the basal ganglia leads to widespread cognitive decline. If transplantation therapy is to succeed in replacing degenerating neurones in HD and reinstating controlled function of complex basal gan-glia circuitry, the new neurones must be able to develop specific long-distance projections that can form accurate and functional connections with neurones in precise target regions. Our ongoing studies are aimed at addressing how we can improve the function of striatal transplants, in particular to optimise the reformation of precise long-distance connections and to re-establish normal motor and cognitive function. In particular, we have investigated optimal requirements for embryonic primary tissue to achieve these aims, and also the potential of other cell sources to provide long-distance projection neurones and reconnect complex circuitry. This review describes current progress of experiments to optimise the reconstruction of neuronal circuitry using primary embryonic tissue transplants, as well as our current initiatives to use neural stem cells or precursors to replace long distance projection neurones in the degenerating basal ganglia. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
neural progenitors, striatum, Huntington’s Disease, connectivity, function, behaviour, neuronal differentiation, transplantation
in
Restorative Neurology and Neuroscience
volume
19
issue
1-2
pages
119 - 138
publisher
IOS Press
external identifiers
  • pmid:12082233
  • scopus:0035553923
ISSN
1878-3627
language
English
LU publication?
yes
id
e44182aa-e86c-4bdb-ad32-4add78c333fa (old id 1121226)
date added to LUP
2008-06-27 13:32:04
date last changed
2018-05-29 12:32:09
@article{e44182aa-e86c-4bdb-ad32-4add78c333fa,
  abstract     = {During the last 30 years, the promise of neural transplantation as a therapeutic strategy for neurodegenerative disease has been slowly recognised. Across the world, clinical transplants of embryonic primary dopamine neurones have been shown to ameliorate some of the motor deficits in Parkinson s disease (PD) patients, and more recently, systematic clinical trials have been initiated for the replacement of striatal projection neurones lost in Huntington's disease (HD). Clinical transplantation as a prospective therapy for HD poses a particular set of difficulties. The hallmarks of this neurodegenerative disease include extensive loss of medium spiny long-distance projection neurones of the caudate and putamen, affecting downstream target nuclei, the globus pallidus and substantia nigra, leading to dysregulation of motor control. In addition, extensive loss of cortical neurones that form the afferent systems to the basal ganglia leads to widespread cognitive decline. If transplantation therapy is to succeed in replacing degenerating neurones in HD and reinstating controlled function of complex basal gan-glia circuitry, the new neurones must be able to develop specific long-distance projections that can form accurate and functional connections with neurones in precise target regions. Our ongoing studies are aimed at addressing how we can improve the function of striatal transplants, in particular to optimise the reformation of precise long-distance connections and to re-establish normal motor and cognitive function. In particular, we have investigated optimal requirements for embryonic primary tissue to achieve these aims, and also the potential of other cell sources to provide long-distance projection neurones and reconnect complex circuitry. This review describes current progress of experiments to optimise the reconstruction of neuronal circuitry using primary embryonic tissue transplants, as well as our current initiatives to use neural stem cells or precursors to replace long distance projection neurones in the degenerating basal ganglia.},
  author       = {Fricker-Gates, Rosemary A. and Lundberg, Cecilia and Dunnett, Stephen B.},
  issn         = {1878-3627},
  keyword      = {neural progenitors,striatum,Huntington’s Disease,connectivity,function,behaviour,neuronal differentiation,transplantation},
  language     = {eng},
  number       = {1-2},
  pages        = {119--138},
  publisher    = {IOS Press},
  series       = {Restorative Neurology and Neuroscience},
  title        = {Neural transplantation: restoring complex circuitry in the striatum},
  volume       = {19},
  year         = {2001},
}