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Survival, differentiation, and connectivity of ventral mesencephalic dopamine neurons following transplantation

Thompson, Lachlan LU and Björklund, Anders LU (2012) In Progress in brain research 200. p.61-95
Abstract

The reconstruction of midbrain dopamine (DA) circuitry through intracerebral transplantation of new DA neurons contained in embryonic ventral mesencephalon (VM) is a promising therapeutic approach for Parkinson's disease (PD). Although some of the early open-label trials have provided proof-of-principal that VM grafts can provide sustained improvement of motor function in some patients, subsequent trials showed that the functional response can be highly variable. This chapter reviews an extensive body of basic and clinical research on the survival, differentiation, and connectivity of DA neurons in VM grafts, and also looks at how these parameters are affected by certain host- and donor-specific variables. We also review how technical... (More)

The reconstruction of midbrain dopamine (DA) circuitry through intracerebral transplantation of new DA neurons contained in embryonic ventral mesencephalon (VM) is a promising therapeutic approach for Parkinson's disease (PD). Although some of the early open-label trials have provided proof-of-principal that VM grafts can provide sustained improvement of motor function in some patients, subsequent trials showed that the functional response can be highly variable. This chapter reviews an extensive body of basic and clinical research on the survival, differentiation, and connectivity of DA neurons in VM grafts, and also looks at how these parameters are affected by certain host- and donor-specific variables. We also review how technical advances in the tools available to study the integration of grafted DA neurons, such as transgenic reporter mice, have made significant contributions to our understanding of the capacity of different DA neuronal subtypes for target-directed growth and innervation of appropriate host brain structures. Our established and on-going understanding of the capacity of grafted DA neurons to structurally and functionally integrate following transplantation forms an important basis for the refinement and optimization of VM grafting procedures, and also the development of new procedures based on the use of stem cells.

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Please use this url to cite or link to this publication:
author
organization
publishing date
type
Chapter in Book/Report/Conference proceeding
publication status
published
subject
keywords
Animals, Brain Tissue Transplantation, Cell Differentiation, Cell Survival, Dopaminergic Neurons, Gene Expression Regulation, Humans, Mesencephalon, Mice, Nervous System Diseases, Neural Pathways, Journal Article, Review
in
Progress in brain research
editor
Dunnett, S. B. ; Björklund, Anders; and
volume
200
pages
35 pages
publisher
Elsevier
external identifiers
  • scopus:84870279696
ISSN
0079-6123
ISBN
978-0-444-59575-1
DOI
10.1016/B978-0-444-59575-1.00004-1
language
English
LU publication?
yes
id
ea7674e0-ea16-4ef8-bb22-f51d70704b33
date added to LUP
2016-11-23 14:10:28
date last changed
2017-11-05 05:10:56
@inbook{ea7674e0-ea16-4ef8-bb22-f51d70704b33,
  abstract     = {<p>The reconstruction of midbrain dopamine (DA) circuitry through intracerebral transplantation of new DA neurons contained in embryonic ventral mesencephalon (VM) is a promising therapeutic approach for Parkinson's disease (PD). Although some of the early open-label trials have provided proof-of-principal that VM grafts can provide sustained improvement of motor function in some patients, subsequent trials showed that the functional response can be highly variable. This chapter reviews an extensive body of basic and clinical research on the survival, differentiation, and connectivity of DA neurons in VM grafts, and also looks at how these parameters are affected by certain host- and donor-specific variables. We also review how technical advances in the tools available to study the integration of grafted DA neurons, such as transgenic reporter mice, have made significant contributions to our understanding of the capacity of different DA neuronal subtypes for target-directed growth and innervation of appropriate host brain structures. Our established and on-going understanding of the capacity of grafted DA neurons to structurally and functionally integrate following transplantation forms an important basis for the refinement and optimization of VM grafting procedures, and also the development of new procedures based on the use of stem cells.</p>},
  author       = {Thompson, Lachlan and Björklund, Anders},
  editor       = {Dunnett, S. B.  and Björklund, Anders},
  isbn         = {978-0-444-59575-1 },
  issn         = {0079-6123},
  keyword      = {Animals,Brain Tissue Transplantation,Cell Differentiation,Cell Survival,Dopaminergic Neurons,Gene Expression Regulation,Humans,Mesencephalon,Mice,Nervous System Diseases,Neural Pathways,Journal Article,Review},
  language     = {eng},
  pages        = {61--95},
  publisher    = {Elsevier},
  series       = {Progress in brain research},
  title        = {Survival, differentiation, and connectivity of ventral mesencephalic dopamine neurons following transplantation},
  url          = {http://dx.doi.org/10.1016/B978-0-444-59575-1.00004-1},
  volume       = {200},
  year         = {2012},
}