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Region-specific restoration of striatal synaptic plasticity by dopamine grafts in experimental parkinsonism.

Rylander, Daniella LU ; Bagetta, Vincenza ; Pendolino, Valentina ; Zianni, Elisa ; Grealish, Shane LU ; Gardoni, Fabrizio ; Di Luca, Monica ; Calabresi, Paolo ; Cenci Nilsson, Angela LU and Picconi, Barbara (2013) In Proceedings of the National Academy of Sciences 110(46). p.4375-4384
Abstract
Intrastriatal transplantation of dopaminergic neurons can restore striatal dopamine levels and improve parkinsonian deficits, but the mechanisms underlying these effects are poorly understood. Here, we show that transplants of dopamine neurons partially restore activity-dependent synaptic plasticity in the host striatal neurons. We evaluated synaptic plasticity in regions distal or proximal to the transplant (i.e., dorsolateral and ventrolateral striatum) and compared the effects of dopamine- and serotonin-enriched grafts using a rat model of Parkinson disease. Naïve rats showed comparable intrinsic membrane properties in the two subregions but distinct patterns of long-term synaptic plasticity. The ventrolateral striatum showed long-term... (More)
Intrastriatal transplantation of dopaminergic neurons can restore striatal dopamine levels and improve parkinsonian deficits, but the mechanisms underlying these effects are poorly understood. Here, we show that transplants of dopamine neurons partially restore activity-dependent synaptic plasticity in the host striatal neurons. We evaluated synaptic plasticity in regions distal or proximal to the transplant (i.e., dorsolateral and ventrolateral striatum) and compared the effects of dopamine- and serotonin-enriched grafts using a rat model of Parkinson disease. Naïve rats showed comparable intrinsic membrane properties in the two subregions but distinct patterns of long-term synaptic plasticity. The ventrolateral striatum showed long-term potentiation using the same protocol that elicited long-term depression in the dorsolateral striatum. The long-term potentiation was linked to higher expression of postsynaptic AMPA and N2B NMDA subunits (GluN2B) and was dependent on the activation of GluN2A and GluN2B subunits and the D1 dopamine receptor. In both regions, the synaptic plasticity was abolished after a severe dopamine depletion and could not be restored by grafted serotonergic neurons. Solely, dopamine-enriched grafts could restore the long-term potentiation and partially restore motor deficits in the rats. The restoration could only be seen close to the graft, in the ventrolateral striatum where the graft-derived reinnervation was denser, compared with the distal dorsolateral region. These data provide proof of concept that dopamine-enriched transplants are able to functionally integrate into the host brain and restore deficits in striatal synaptic plasticity after experimental parkinsonism. The region-specific restoration might impose limitations in symptomatic improvement following neural transplantation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences
volume
110
issue
46
pages
4375 - 4384
publisher
National Acad Sciences
external identifiers
  • wos:000326830900017
  • pmid:24170862
  • scopus:84887480169
  • pmid:24170862
ISSN
1091-6490
DOI
10.1073/pnas.1311187110
language
English
LU publication?
yes
id
926a334a-cda7-4f72-8a01-28fbc45e6308 (old id 4142868)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24170862?dopt=Abstract
date added to LUP
2016-04-01 10:17:21
date last changed
2020-01-07 01:58:36
@article{926a334a-cda7-4f72-8a01-28fbc45e6308,
  abstract     = {Intrastriatal transplantation of dopaminergic neurons can restore striatal dopamine levels and improve parkinsonian deficits, but the mechanisms underlying these effects are poorly understood. Here, we show that transplants of dopamine neurons partially restore activity-dependent synaptic plasticity in the host striatal neurons. We evaluated synaptic plasticity in regions distal or proximal to the transplant (i.e., dorsolateral and ventrolateral striatum) and compared the effects of dopamine- and serotonin-enriched grafts using a rat model of Parkinson disease. Naïve rats showed comparable intrinsic membrane properties in the two subregions but distinct patterns of long-term synaptic plasticity. The ventrolateral striatum showed long-term potentiation using the same protocol that elicited long-term depression in the dorsolateral striatum. The long-term potentiation was linked to higher expression of postsynaptic AMPA and N2B NMDA subunits (GluN2B) and was dependent on the activation of GluN2A and GluN2B subunits and the D1 dopamine receptor. In both regions, the synaptic plasticity was abolished after a severe dopamine depletion and could not be restored by grafted serotonergic neurons. Solely, dopamine-enriched grafts could restore the long-term potentiation and partially restore motor deficits in the rats. The restoration could only be seen close to the graft, in the ventrolateral striatum where the graft-derived reinnervation was denser, compared with the distal dorsolateral region. These data provide proof of concept that dopamine-enriched transplants are able to functionally integrate into the host brain and restore deficits in striatal synaptic plasticity after experimental parkinsonism. The region-specific restoration might impose limitations in symptomatic improvement following neural transplantation.},
  author       = {Rylander, Daniella and Bagetta, Vincenza and Pendolino, Valentina and Zianni, Elisa and Grealish, Shane and Gardoni, Fabrizio and Di Luca, Monica and Calabresi, Paolo and Cenci Nilsson, Angela and Picconi, Barbara},
  issn         = {1091-6490},
  language     = {eng},
  number       = {46},
  pages        = {4375--4384},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Region-specific restoration of striatal synaptic plasticity by dopamine grafts in experimental parkinsonism.},
  url          = {http://dx.doi.org/10.1073/pnas.1311187110},
  doi          = {10.1073/pnas.1311187110},
  volume       = {110},
  year         = {2013},
}