Document Detail


Neurochemical changes in a double transgenic mouse model of Alzheimer's disease fed a pro-oxidant diet.
MedLine Citation:
PMID:  20600435     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oxidative stress is implicated in the pathogenesis of Alzheimer's disease (AD) causing neurodegeneration and decreased monoamine neurotransmitters. We investigated the effect of administration of a pro-oxidant diet on the levels of monoamines and metabolites in the brains of wildtype and transgenic mice expressing mutant APP and PS-1 (TASTPM mice). Three-month-old TASTPM and wildtype (C57BL6/J) mice were fed either normal or pro-oxidant diet for 3 months. The neocortex, cerebellum, hippocampus and striatum were assayed for their monoamine and monoamine metabolite content using HPLC with electrochemical detection. Striatal tyrosine hydroxylase (TOH) levels were analysed by Western blotting. In the striatum, female TASTPM mice had higher levels of DOPAC and male TASTPM mice had higher levels of 5-HIAA compared to wildtype mice. Administration of pro-oxidant diet increased striatal MHPG, turnover of NA and 5-HT levels in female TASTPM mice compared to TASTPM mice fed control diet. The pro-oxidant diet also decreased DOPAC levels in female TASTPM mice compared to those fed control diet. Striatal TOH did not depend on diet, gender or genotype. In the neocortex, the TASTPM genotype increased levels of 5-HIAA in male mice fed control diet compared to wildtype mice. In the cerebellum, the TASTPM genotype led to decreased levels of HVA (male mice only) and also decreased turnover of DA (female mice only) compared to wildtype mice. These data suggest a sparing of monoaminergic neurones in the cortex, striatum and hippocampus of TASTPM mice fed pro-oxidant diet and could be indicative of increased activity in corticostriatal circuits. The decreased cerebellar levels of HVA and turnover of DA in TASTPM mice hint at possible axonal degeneration within this subregion.
Authors:
Elizabeth S Ash; Mohammad S Alavijeh; Alan M Palmer; Cathy Mitchelmore; David R Howlett; Paul T Francis; Martin Broadstock; Jill C Richardson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-30
Journal Detail:
Title:  Neurochemistry international     Volume:  57     ISSN:  1872-9754     ISO Abbreviation:  Neurochem. Int.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-09-06     Completed Date:  2010-12-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  504-11     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Pharmidex Pharmaceutical Services Ltd., London, UK. E.Ash@Pharmidex.com
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MeSH Terms
Descriptor/Qualifier:
Alzheimer Disease / genetics,  metabolism*
Amyloid beta-Protein Precursor / genetics,  metabolism
Animals
Biogenic Monoamines / metabolism
Blotting, Western
Brain Chemistry / drug effects
Chromatography, High Pressure Liquid
Diet*
Female
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neurotransmitter Agents / metabolism
Oxidants / pharmacology*
Oxidative Stress / drug effects,  physiology
Presenilins / genetics,  metabolism
Reference Standards
Transgenes
Tyrosine 3-Monooxygenase / metabolism
Chemical
Reg. No./Substance:
0/Amyloid beta-Protein Precursor; 0/Biogenic Monoamines; 0/Neurotransmitter Agents; 0/Oxidants; 0/Presenilins; EC 1.14.16.2/Tyrosine 3-Monooxygenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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