Advanced

Regulation of neuropeptide mRNA expression in the basal ganglia by intrastriatal and intranigral transplants in the rat Parkinson model.

Winkler, Christian LU ; Bentlage, C; Cenci, M A; Nikkhah, G and Björklund, Anders LU (2003) In Neuroscience 118(4). p.1063-1077
Abstract
Previous studies have shown that intrastriatal transplants of dopamine (DA)-rich fetal ventral mesencephalic (VM) tissue can correct denervation-induced changes in the cellular expression of neuropeptide and receptor mRNAs in the rat Parkinson model. However, with the standard transplantation approach normalization of all cellular parameters has not been obtained. This may be due either to the incomplete striatal reinnervation achieved by these transplants, or to the ectopic placement of the grafts. In the present study we have used a microtransplantation approach to obtain a more complete reinnervation of the denervated striatum (20 micrograft deposits spread over the entire structure). Neurons were also implanted directly into the... (More)
Previous studies have shown that intrastriatal transplants of dopamine (DA)-rich fetal ventral mesencephalic (VM) tissue can correct denervation-induced changes in the cellular expression of neuropeptide and receptor mRNAs in the rat Parkinson model. However, with the standard transplantation approach normalization of all cellular parameters has not been obtained. This may be due either to the incomplete striatal reinnervation achieved by these transplants, or to the ectopic placement of the grafts. In the present study we have used a microtransplantation approach to obtain a more complete reinnervation of the denervated striatum (20 micrograft deposits spread over the entire structure). Neurons were also implanted directly into the substantia nigra. In rats with multiple intrastriatal VM transplants the lesion-induced upregulation of mRNAs encoding for preproenkephalin (PPE), the D2-type DA-receptor, and the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD67) was normalized throughout the striatum, whereas the lesion-induced downregulation of preprotachykinin mRNA was unaffected. Intranigral grafts of either fetal DA-rich VM tissue or GABA-rich striatal tissue did not induce any changes in striatal neuropeptide and D2-receptor mRNA expression despite significant behavioral improvement. Comparison of the behavioral data with levels of neuropeptide expression showed that in rats with intrastriatal VM transplants a complete normalization of striatal PPE and GAD67 mRNA expression did not translate into a complete recovery of spontaneous motor behaviors. The results show that extensive DA reinnervation of the host striatum by multiple VM microtransplants is insufficient to obtain full recovery of all lesion-induced changes at both the cellular and the behavioral level. A full reconstruction of the nigrostriatal pathway or, alternatively, modulation of basal ganglia function by grafting in non-striatal regions may be required to further improve the functional outcome in the DA-denervated brain. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
D2-receptor, transplantation, preproenkephalin, GABA, GAD, preprotachykinin
in
Neuroscience
volume
118
issue
4
pages
1063 - 1077
publisher
Elsevier
external identifiers
  • pmid:12732251
  • wos:000182926900018
  • scopus:0037728902
ISSN
1873-7544
DOI
10.1016/S0306-4522(03)00007-1
language
English
LU publication?
yes
id
7451355c-45bb-4f36-ae0e-71cbecaca1d1 (old id 114205)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12732251&dopt=Abstract
date added to LUP
2007-06-26 13:19:56
date last changed
2018-01-07 06:03:59
@article{7451355c-45bb-4f36-ae0e-71cbecaca1d1,
  abstract     = {Previous studies have shown that intrastriatal transplants of dopamine (DA)-rich fetal ventral mesencephalic (VM) tissue can correct denervation-induced changes in the cellular expression of neuropeptide and receptor mRNAs in the rat Parkinson model. However, with the standard transplantation approach normalization of all cellular parameters has not been obtained. This may be due either to the incomplete striatal reinnervation achieved by these transplants, or to the ectopic placement of the grafts. In the present study we have used a microtransplantation approach to obtain a more complete reinnervation of the denervated striatum (20 micrograft deposits spread over the entire structure). Neurons were also implanted directly into the substantia nigra. In rats with multiple intrastriatal VM transplants the lesion-induced upregulation of mRNAs encoding for preproenkephalin (PPE), the D2-type DA-receptor, and the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD67) was normalized throughout the striatum, whereas the lesion-induced downregulation of preprotachykinin mRNA was unaffected. Intranigral grafts of either fetal DA-rich VM tissue or GABA-rich striatal tissue did not induce any changes in striatal neuropeptide and D2-receptor mRNA expression despite significant behavioral improvement. Comparison of the behavioral data with levels of neuropeptide expression showed that in rats with intrastriatal VM transplants a complete normalization of striatal PPE and GAD67 mRNA expression did not translate into a complete recovery of spontaneous motor behaviors. The results show that extensive DA reinnervation of the host striatum by multiple VM microtransplants is insufficient to obtain full recovery of all lesion-induced changes at both the cellular and the behavioral level. A full reconstruction of the nigrostriatal pathway or, alternatively, modulation of basal ganglia function by grafting in non-striatal regions may be required to further improve the functional outcome in the DA-denervated brain.},
  author       = {Winkler, Christian and Bentlage, C and Cenci, M A and Nikkhah, G and Björklund, Anders},
  issn         = {1873-7544},
  keyword      = {D2-receptor,transplantation,preproenkephalin,GABA,GAD,preprotachykinin},
  language     = {eng},
  number       = {4},
  pages        = {1063--1077},
  publisher    = {Elsevier},
  series       = {Neuroscience},
  title        = {Regulation of neuropeptide mRNA expression in the basal ganglia by intrastriatal and intranigral transplants in the rat Parkinson model.},
  url          = {http://dx.doi.org/10.1016/S0306-4522(03)00007-1},
  volume       = {118},
  year         = {2003},
}