Regional selectivity of amyloid mRNA expression and neurotrophins on repetitive inhibition of oxidative phosphorylation.
Previously we showed that repetitive inhibition of oxidative phosphorylation impairs synaptic transmission and induces overexpression of amyloid precursor protein mRNA (APP-mRNA) in the hippocampus (Hellweg et al., 2003). Here we show that APP-mRNA remains alike in murine frontal cortex and cerebellum on repetitive treatment with 3-nitropropionate. However, nerve growth factor and brain-derived neurotrophic factor decreased by 28 to 38% in frontal cortex. Taken together, the pattern of change resembles genetic models of Alzheimer's disease with less susceptibility for overexpression of amyloid mRNA in frontal cortex than in hippocampus and reduced neurotrophin levels in frontal cortex. Given the similarity of this pattern to the one observed in human Alzheimer's disease the present model in future may give further insight into the pathophysiology of sporadic Alzheimer's disease.
von Arnim
C A F
CA
Department of Neurology, University of Ulm, Germany.
Hellweg
R
R
Büchner
M
M
Huber
R
R
Riepe
M W
MW
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D002534:Hypoxia, Brain / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D020932:Nerve Growth Factor / Q000187:drug effects / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D009574:Nitro Compounds; D010085:Oxidative Phosphorylation / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D019208:Brain-Derived Neurotrophic Factor; D003292:Convulsants; D009414:Nerve Growth Factors; D009574:Nitro Compounds; D011422:Propionates; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D013385:Succinate Dehydrogenase; C015392:3-nitropropionic acid