| Neuroprotective effect of PACAP on translational control alteration and cognitive decline in MPTP parkinsonian mice. | |
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MedLine Citation:
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PMID: 19626386 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Parkinson's disease (PD) is characterized by a triade of motor symptoms due to the degeneration of nigrostriatal pathway. In addition to these motor impairments, cognitive disturbances have been reported to occur in PD patients in the early stage of the disease. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin widely used to produce experimental models of PD. In a previous work, we showed that MPTP altered the expression of proteins involved in mTOR antiapoptotic and PKR apoptotic pathways of translational control (TC) in neuroblastoma cells. In the present study, the results indicated that a subchronic MPTP intoxication in mice decreased the dopaminergic neuron number, produced an activation of PKR way and an inhibition of mTOR way of TC especially in striatum and frontal cortex associated with a great activation of PKR in hippocampus. Moreover, in parallel to biochemical analysis, the mnesic disturbances induced by MPTP were characterized in C57Bl/6 mice, by testing their performance in three versions of the Morris Water Maze task. Behavioral results showed that the MPTP lesion altered mice learning of a spatial working memory, of a cued version and of a spatial reference memory task in the water maze. Furthermore, we previously demonstrated that the neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) could counteract the MPTP toxicity on TC factors in neuroblastoma cells. Thus, the second objective of our study was to assess the PACAP effect on MPTP-induced TC impairment and cognitive deficit in mice. The pretreatment with PACAP27 by intravenous injections partially protected TH-positive neuron loss induced by MPTP, prevented the MPTP-induced protein synthesis control dysregulation and mnesic impairment of mice. Therefore, our results could indicate that PACAP may be a promising therapeutic agent in Parkinson's disease. |
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Authors:
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Julie Deguil; Fran?ois Chavant; Claire Lafay-Chebassier; Marie-Christine P?rault-Pochat; Bernard Fauconneau; St?phanie Pain |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-07-21 |
Journal Detail:
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Title: Neurotoxicity research Volume: 17 ISSN: 1476-3524 ISO Abbreviation: Neurotox Res Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2009-12-24 Completed Date: 2010-03-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100929017 Medline TA: Neurotox Res Country: United States |
Other Details:
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Languages: eng Pagination: 142-55 Citation Subset: IM |
Affiliation:
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Research Group on Brain Aging, GReViC, EA 3808, P?le de Biologie Sant?, University of Poitiers, Poitiers cedex, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Count / methods Cognition / drug effects* Cognition Disorders / drug therapy, etiology*, pathology Cues Disease Models, Animal Drug Interactions Gene Expression Regulation / drug effects* Injections, Intravenous / methods Intracellular Signaling Peptides and Proteins / metabolism MPTP Poisoning / complications*, drug therapy, pathology Male Maze Learning / drug effects Memory / drug effects Mice Mice, Inbred C57BL Neuroprotective Agents / pharmacology* Pituitary Adenylate Cyclase-Activating Polypeptide / pharmacology*, therapeutic use Protein-Serine-Threonine Kinases / metabolism Receptors, G-Protein-Coupled / metabolism Signal Transduction / drug effects Space Perception / drug effects Time Factors Tyrosine 3-Monooxygenase / metabolism Visual Perception / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Intracellular Signaling Peptides and Proteins; 0/Neuroprotective Agents; 0/Pituitary Adenylate Cyclase-Activating Polypeptide; 0/Receptors, G-Protein-Coupled; EC 1.14.16.2/Tyrosine 3-Monooxygenase; EC 2.7.1.-/mTOR protein; EC 2.7.11.1/Protein-Serine-Threonine Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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