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Neuroprotection in Parkinson models varies with toxin administration protocol.
Eur J Neurosci. 2006 Dec; 24(11):3174-82.EJ

Abstract

Numerous factors contribute to substantia nigra pars compacta (SNc) dopamine (DA) neuron death in Parkinson's disease (PD), thus complicating the search for effective neuroprotective agents for this disease. Although the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse has been widely used for assessing neuroprotective agents for PD, the pathological processes resulting from MPTP exposure can vary greatly depending upon the MPTP administration protocol. This study assessed the degree to which the neuroprotective efficacy of particular agents may depend upon the MPTP administration protocol (i.e. acute vs. subacute toxin administration). Endpoints analysed were changes in tyrosine hydroxylase (TH) and NeuN cell numbers in the SNc, striatal DA and metabolite levels, and striatal TH+ fiber density. The efficacy of putative neuroprotective agents [i.e. LIGA 20, nicotinamide and pramipexole (PPX)] varied depending upon the MPTP administration protocol. LIGA 20 spared striatal DA levels in both MPTP models, while nicotinamide was only effective in the acute toxin administration model and PPX was only effective in the subacute model. In both MPTP models, LIGA 20 and nicotinamide significantly spared DAergic neurons; PPX only spared DAergic neurons in the subacute model. Only acute MPTP-treated mice that received nicotinamide had a significant sparing of striatal DAergic fibers. These results underscore the need to assess putative neuroprotective agents for PD in multiple animal models using multiple endpoints. This strategy may better identify compounds with broad neuroprotective/neurorestorative profiles that may be more likely to be clinically effective.

Authors+Show Affiliations

Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia PA 19107, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17156378

Citation

Anderson, David W., et al. "Neuroprotection in Parkinson Models Varies With Toxin Administration Protocol." The European Journal of Neuroscience, vol. 24, no. 11, 2006, pp. 3174-82.
Anderson DW, Bradbury KA, Schneider JS. Neuroprotection in Parkinson models varies with toxin administration protocol. Eur J Neurosci. 2006;24(11):3174-82.
Anderson, D. W., Bradbury, K. A., & Schneider, J. S. (2006). Neuroprotection in Parkinson models varies with toxin administration protocol. The European Journal of Neuroscience, 24(11), 3174-82.
Anderson DW, Bradbury KA, Schneider JS. Neuroprotection in Parkinson Models Varies With Toxin Administration Protocol. Eur J Neurosci. 2006;24(11):3174-82. PubMed PMID: 17156378.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotection in Parkinson models varies with toxin administration protocol. AU - Anderson,David W, AU - Bradbury,Kristin A, AU - Schneider,Jay S, PY - 2006/12/13/pubmed PY - 2007/2/24/medline PY - 2006/12/13/entrez SP - 3174 EP - 82 JF - The European journal of neuroscience JO - Eur J Neurosci VL - 24 IS - 11 N2 - Numerous factors contribute to substantia nigra pars compacta (SNc) dopamine (DA) neuron death in Parkinson's disease (PD), thus complicating the search for effective neuroprotective agents for this disease. Although the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse has been widely used for assessing neuroprotective agents for PD, the pathological processes resulting from MPTP exposure can vary greatly depending upon the MPTP administration protocol. This study assessed the degree to which the neuroprotective efficacy of particular agents may depend upon the MPTP administration protocol (i.e. acute vs. subacute toxin administration). Endpoints analysed were changes in tyrosine hydroxylase (TH) and NeuN cell numbers in the SNc, striatal DA and metabolite levels, and striatal TH+ fiber density. The efficacy of putative neuroprotective agents [i.e. LIGA 20, nicotinamide and pramipexole (PPX)] varied depending upon the MPTP administration protocol. LIGA 20 spared striatal DA levels in both MPTP models, while nicotinamide was only effective in the acute toxin administration model and PPX was only effective in the subacute model. In both MPTP models, LIGA 20 and nicotinamide significantly spared DAergic neurons; PPX only spared DAergic neurons in the subacute model. Only acute MPTP-treated mice that received nicotinamide had a significant sparing of striatal DAergic fibers. These results underscore the need to assess putative neuroprotective agents for PD in multiple animal models using multiple endpoints. This strategy may better identify compounds with broad neuroprotective/neurorestorative profiles that may be more likely to be clinically effective. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/17156378/Neuroprotection_in_Parkinson_models_varies_with_toxin_administration_protocol_ DB - PRIME DP - Unbound Medicine ER -