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P2‐170: Suppression of Different Genes by Irna in a DROSOPHILA Model and their Possible Relation to the Pathology of Alzheimer’s Disease: Bottom‐Up Proteomics of Alzheimer’s Disease Brains and Validation in DROSOPHILA Models
Author(s) -
Minjarez Benito D.,
Rodriguez-Yañez Yury,
Haramati Jesse,
Luna-Arias Juan Pedro,
Rincon-Limas Diego E.
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.1337
Subject(s) - proteome , proteomics , phenotype , disease , dementia , biology , drosophila melanogaster , alzheimer's disease , neuroscience , bioinformatics , genetics , gene , pathology , medicine
Background: Previous evidence of IMI PharmaCog project (Grant Agreement n 115009, www.pharmacog.org) showed that delta (16 Hz) and theta (6-10 Hz) ongoing electroencephalographic (EEG) rhythms differed between freely behaving C57 wild-type (WT) and transgenic mouse models Alzheimer’s disease (AD) characterized by accumulation of Ab42 in the brain, i.e. the TASTPM mice. Here, we tested whether these EEG rhythms reflected the effects of chronic administration of BACE-1 inhibitor in TASTPM compared with WT mice. Methods: In the PharmaCog project, ongoing EEG data were recorded from a frontoparietal bipolar channel in 13 WT Vehicle, 12 WT BACE-1, 12 TASTPM Vehicle, and 13 TASTPM BACE-1 mice (males; aged 8/9 months old at the beginning of treatment). All mice underwent to daily administration of 10 mg/kg of BACE-1 or Vehicle (placebo) through tube feeding for four weeks. Artifact-free EEG power density was compared between the first day (Day 0) and after four weeks (Week 4) of the drug administration. o-bidi-language:ARSA;mso-bidi-font-weight:bold’>, i.e. the TASTPM mice. Here, we tested whether these EEG rhythms reflected the effects of chronic administration of BACE-1 inhibitor in TASTPM compared withWTmice.Results:In the Day 0, 2-8 Hz EEG power density was lower in TASTPM than WT mice as a reference of “normal” EEG activity (p<0.05). In this framework, chronic BACE-1 inhibitor administration for four weeks induced a significant decrease (p<0.05) of 2-10 Hz EEG power density in the TASTPM but not the WT mice (Fig. 1). Conclusions:Ongoing EEG rhythms characterized TASTPM mice before and after the chronic administration of BACE-1 inhibition for four weeks. The effects of BACE-1 on the TASTPM mice were not in the direction of a “normalization” of EEG power density. This finding unveiled the neurophysiological effect of BACE-1 on cortical arousal and enriched the “go-no go” decision-making process about the use of this drug in clinical research.