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Non-dopaminergic neurons in ventral mesencephalic transplants make widespread axonal connections in the host brain.

Thompson, Lachlan LU ; Kirik, Deniz LU and Björklund, Anders LU (2008) In Experimental Neurology 213. p.220-228
Abstract
Motor dysfunction in Parkinson's disease (PD) can be effectively alleviated through intra-striatal transplantation of fetal ventral mesencephalic tissue. The success of this approach is dependent on the survival, axonal outgrowth and synaptic integration of newly grafted dopamine neurons with the host striatum. The functional outcome of transplantation therapy has, however, been highly variable, particularly in PD patients, but also in animal models of PD, and thus there is a need for a deeper understanding of possible mechanisms underlying this variability such as graft composition and the resulting graft-host connectivity. Here we describe a series of transplantation experiments whereby mouse VM tissue has been grafted into the striatum... (More)
Motor dysfunction in Parkinson's disease (PD) can be effectively alleviated through intra-striatal transplantation of fetal ventral mesencephalic tissue. The success of this approach is dependent on the survival, axonal outgrowth and synaptic integration of newly grafted dopamine neurons with the host striatum. The functional outcome of transplantation therapy has, however, been highly variable, particularly in PD patients, but also in animal models of PD, and thus there is a need for a deeper understanding of possible mechanisms underlying this variability such as graft composition and the resulting graft-host connectivity. Here we describe a series of transplantation experiments whereby mouse VM tissue has been grafted into the striatum of 6-hydroxydopamine lesioned rats. Six weeks after grafting immunohistochemical analysis using the mouse specific 'M2M6' antibodies revealed both dopaminergic and non-dopaminergic components of graft-derived fibre outgrowth into the host brain. We report here that while dopaminergic outgrowth was predominately confined to the striatum, there was also a significant degree of non-dopaminergic outgrowth to extra-striatal structures including the thalamus, cortex and midbrain. Retrograde tracing experiments showed that grafted neurons of GABAergic identity contribute to this non-dopaminergic outgrowth. In line with our recent findings on the function of serotonergic neurons in fetal VM grafts, these results further underscore the potential impact that non-dopaminergic neurons may have on the functional outcome of intrastriatal fetal VM grafts. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Experimental Neurology
volume
213
pages
220 - 228
publisher
Academic Press
external identifiers
  • wos:000258943500027
  • pmid:18602916
  • scopus:49549087079
ISSN
0014-4886
DOI
10.1016/j.expneurol.2008.06.005
language
English
LU publication?
yes
id
920b4a4e-0587-4e39-8546-7709d815ab96 (old id 1181525)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18602916?dopt=Abstract
date added to LUP
2008-08-06 11:44:11
date last changed
2017-05-07 04:28:09
@article{920b4a4e-0587-4e39-8546-7709d815ab96,
  abstract     = {Motor dysfunction in Parkinson's disease (PD) can be effectively alleviated through intra-striatal transplantation of fetal ventral mesencephalic tissue. The success of this approach is dependent on the survival, axonal outgrowth and synaptic integration of newly grafted dopamine neurons with the host striatum. The functional outcome of transplantation therapy has, however, been highly variable, particularly in PD patients, but also in animal models of PD, and thus there is a need for a deeper understanding of possible mechanisms underlying this variability such as graft composition and the resulting graft-host connectivity. Here we describe a series of transplantation experiments whereby mouse VM tissue has been grafted into the striatum of 6-hydroxydopamine lesioned rats. Six weeks after grafting immunohistochemical analysis using the mouse specific 'M2M6' antibodies revealed both dopaminergic and non-dopaminergic components of graft-derived fibre outgrowth into the host brain. We report here that while dopaminergic outgrowth was predominately confined to the striatum, there was also a significant degree of non-dopaminergic outgrowth to extra-striatal structures including the thalamus, cortex and midbrain. Retrograde tracing experiments showed that grafted neurons of GABAergic identity contribute to this non-dopaminergic outgrowth. In line with our recent findings on the function of serotonergic neurons in fetal VM grafts, these results further underscore the potential impact that non-dopaminergic neurons may have on the functional outcome of intrastriatal fetal VM grafts.},
  author       = {Thompson, Lachlan and Kirik, Deniz and Björklund, Anders},
  issn         = {0014-4886},
  language     = {eng},
  pages        = {220--228},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Non-dopaminergic neurons in ventral mesencephalic transplants make widespread axonal connections in the host brain.},
  url          = {http://dx.doi.org/10.1016/j.expneurol.2008.06.005},
  volume       = {213},
  year         = {2008},
}