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Unilateral axonal or terminal injection of 6-hydroxydopamine causes rapid-onset nigrostriatal degeneration and contralateral motor impairments in the rat.

Grealish, Shane LU ; Xie, Lan; Kelly, Maebh and Dowd, Eilís (2008) In Brain Research Bulletin 77. p.312-319
Abstract
Unilateral injection of the catecholamine neurotoxin 6-hydroxydopamine into the axons or terminals of the nigrostriatal pathway is commonly used to model Parkinson's disease in experimental animals. Although the terminal lesion paradigm is considered to induce a more progressive lesion when compared to the axonal lesion, few studies have directly compared the early time-course for lesion development in these two models. Thus, this experiment is sought to establish the temporal pattern of nigrostriatal degeneration and emergence of contralateral motor impairment in these models. Young adult male Lister Hooded rats were used. After baseline testing on a battery of spontaneous motor tests, standard stereotaxic techniques were used to inject... (More)
Unilateral injection of the catecholamine neurotoxin 6-hydroxydopamine into the axons or terminals of the nigrostriatal pathway is commonly used to model Parkinson's disease in experimental animals. Although the terminal lesion paradigm is considered to induce a more progressive lesion when compared to the axonal lesion, few studies have directly compared the early time-course for lesion development in these two models. Thus, this experiment is sought to establish the temporal pattern of nigrostriatal degeneration and emergence of contralateral motor impairment in these models. Young adult male Lister Hooded rats were used. After baseline testing on a battery of spontaneous motor tests, standard stereotaxic techniques were used to inject 6-hydroxydopamine into the nigrostriatal axons or terminals at the level of the medial forebrain bundle or striatum respectively. From the day after lesion surgery, a subset of the rats was tested for motor performance, while another subset was used for immunohistochemical analysis. Quantitative tyrosine hydroxylase immunohistochemistry revealed that although both lesions caused a similar temporal pattern of immunopositive cell loss from the substantia nigra, the terminal lesion caused a more rapid loss of immunopositive terminals from the striatum. Despite these differences in striatal dopaminergic deafferentation, both lesion types caused a profound loss of contralateral motor function from the first day after lesion surgery. These findings illustrate the rapidity of the neuropathological and behavioural consequences of either axonal or terminal injection of 6-hydroxydopamine into the nigrostriatal pathway, and further highlight the need for a more progressive model of human Parkinson's disease. (Less)
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author
organization
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Contribution to journal
publication status
published
subject
in
Brain Research Bulletin
volume
77
pages
312 - 319
publisher
Elsevier
external identifiers
  • wos:000261126400016
  • pmid:18817852
  • scopus:54549119458
ISSN
0361-9230
DOI
10.1016/j.brainresbull.2008.08.018
language
English
LU publication?
yes
id
a7f5f3f6-04c8-4ead-96c5-0aefc793d562 (old id 1242641)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18817852?dopt=Abstract
date added to LUP
2008-10-03 16:09:07
date last changed
2017-01-01 07:32:29
@article{a7f5f3f6-04c8-4ead-96c5-0aefc793d562,
  abstract     = {Unilateral injection of the catecholamine neurotoxin 6-hydroxydopamine into the axons or terminals of the nigrostriatal pathway is commonly used to model Parkinson's disease in experimental animals. Although the terminal lesion paradigm is considered to induce a more progressive lesion when compared to the axonal lesion, few studies have directly compared the early time-course for lesion development in these two models. Thus, this experiment is sought to establish the temporal pattern of nigrostriatal degeneration and emergence of contralateral motor impairment in these models. Young adult male Lister Hooded rats were used. After baseline testing on a battery of spontaneous motor tests, standard stereotaxic techniques were used to inject 6-hydroxydopamine into the nigrostriatal axons or terminals at the level of the medial forebrain bundle or striatum respectively. From the day after lesion surgery, a subset of the rats was tested for motor performance, while another subset was used for immunohistochemical analysis. Quantitative tyrosine hydroxylase immunohistochemistry revealed that although both lesions caused a similar temporal pattern of immunopositive cell loss from the substantia nigra, the terminal lesion caused a more rapid loss of immunopositive terminals from the striatum. Despite these differences in striatal dopaminergic deafferentation, both lesion types caused a profound loss of contralateral motor function from the first day after lesion surgery. These findings illustrate the rapidity of the neuropathological and behavioural consequences of either axonal or terminal injection of 6-hydroxydopamine into the nigrostriatal pathway, and further highlight the need for a more progressive model of human Parkinson's disease.},
  author       = {Grealish, Shane and Xie, Lan and Kelly, Maebh and Dowd, Eilís},
  issn         = {0361-9230},
  language     = {eng},
  pages        = {312--319},
  publisher    = {Elsevier},
  series       = {Brain Research Bulletin},
  title        = {Unilateral axonal or terminal injection of 6-hydroxydopamine causes rapid-onset nigrostriatal degeneration and contralateral motor impairments in the rat.},
  url          = {http://dx.doi.org/10.1016/j.brainresbull.2008.08.018},
  volume       = {77},
  year         = {2008},
}