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Systemic lipopolysaccharide plus MPTP as a model of dopamine loss and gait instability in C57Bl/6J mice

Byler, Stefanie LU ; Boehm, Gary W.; Karp, Jonathan D.; Kohman, Rachel A.; Tarr, Andrew J.; Schallert, Timothy and Barth, Timothy M. (2009) In Behavioural Brain Research 198(2). p.434-439
Abstract
In most environmental models of Parkinson's disease (PD), a single neurodegenerative agent is introduced to cause nigrostriatal clopamine depletion. However, cell loss in human PD often might derive, at least in part. from multiple toxins or vulnerabilities, any one of which alone does not inevitably lead to chronic dopamine depletion. In the present research, male C57BL/6J mice were systemically administered the inflammatory bacterial endotoxin, lipopolysaccharide (LPS) and the neurotoxin 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) alone or in combination and the behavior as well as striatal dopamine levels were compared to saline-treated mice. Mice in the combination (LPS + MPTP) group, but not in the single-factor groups, showed... (More)
In most environmental models of Parkinson's disease (PD), a single neurodegenerative agent is introduced to cause nigrostriatal clopamine depletion. However, cell loss in human PD often might derive, at least in part. from multiple toxins or vulnerabilities, any one of which alone does not inevitably lead to chronic dopamine depletion. In the present research, male C57BL/6J mice were systemically administered the inflammatory bacterial endotoxin, lipopolysaccharide (LPS) and the neurotoxin 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) alone or in combination and the behavior as well as striatal dopamine levels were compared to saline-treated mice. Mice in the combination (LPS + MPTP) group, but not in the single-factor groups, showed both dopamine depletion and parkinsonian symptoms, i.e., reduced stride length, at 4 months post-injection. MPTP alone acutely reduced striatal dopamine levels but this effect was transient as striatal dopamine recovered to normal levels after time (4 months). The LPS-only group showed no dopamine depletion or reduced stride length. These data are consistent with the view that nigrostriatal dopamine neurons might succumb after time to multiple toxic agents that independently may have only a transient, adverse effect. (C) 2008 Elsevier B.V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Inflammation, Stride length, Behavior, LPS, Dopamine loss, MPTP, Parkinson's disease, Animal models
in
Behavioural Brain Research
volume
198
issue
2
pages
434 - 439
publisher
Elsevier
external identifiers
  • wos:000264309800023
  • scopus:59649123336
ISSN
0166-4328
DOI
10.1016/j.bbr.2008.11.027
language
English
LU publication?
yes
id
827c317c-0068-4479-9ead-acb5acdc7398 (old id 1401945)
date added to LUP
2009-06-03 14:33:22
date last changed
2017-09-03 03:55:28
@article{827c317c-0068-4479-9ead-acb5acdc7398,
  abstract     = {In most environmental models of Parkinson's disease (PD), a single neurodegenerative agent is introduced to cause nigrostriatal clopamine depletion. However, cell loss in human PD often might derive, at least in part. from multiple toxins or vulnerabilities, any one of which alone does not inevitably lead to chronic dopamine depletion. In the present research, male C57BL/6J mice were systemically administered the inflammatory bacterial endotoxin, lipopolysaccharide (LPS) and the neurotoxin 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) alone or in combination and the behavior as well as striatal dopamine levels were compared to saline-treated mice. Mice in the combination (LPS + MPTP) group, but not in the single-factor groups, showed both dopamine depletion and parkinsonian symptoms, i.e., reduced stride length, at 4 months post-injection. MPTP alone acutely reduced striatal dopamine levels but this effect was transient as striatal dopamine recovered to normal levels after time (4 months). The LPS-only group showed no dopamine depletion or reduced stride length. These data are consistent with the view that nigrostriatal dopamine neurons might succumb after time to multiple toxic agents that independently may have only a transient, adverse effect. (C) 2008 Elsevier B.V. All rights reserved.},
  author       = {Byler, Stefanie and Boehm, Gary W. and Karp, Jonathan D. and Kohman, Rachel A. and Tarr, Andrew J. and Schallert, Timothy and Barth, Timothy M.},
  issn         = {0166-4328},
  keyword      = {Inflammation,Stride length,Behavior,LPS,Dopamine loss,MPTP,Parkinson's disease,Animal models},
  language     = {eng},
  number       = {2},
  pages        = {434--439},
  publisher    = {Elsevier},
  series       = {Behavioural Brain Research},
  title        = {Systemic lipopolysaccharide plus MPTP as a model of dopamine loss and gait instability in C57Bl/6J mice},
  url          = {http://dx.doi.org/10.1016/j.bbr.2008.11.027},
  volume       = {198},
  year         = {2009},
}