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P1‐274: Ageing increases vulnerability to Aβ42 toxicity in drosophila
Author(s) -
Kerr Fiona,
Rogers Iain,
Martinez Pedro,
Hardy John,
Lovestone Simon,
Partridge Linda
Publication year - 2012
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.2012.05.554
Subject(s) - ageing , neurodegeneration , toxicity , biology , drosophila melanogaster , senescence , proteotoxicity , physiology , toxicology , disease , microbiology and biotechnology , medicine , protein aggregation , genetics , gene
a transgenic animal model of familial AD, namely the PD-APP mouse, over a time frame where Ab42 levels are known to rise. Methods: Experiments were performed in accordance with the Animal (Scientific Procedures) Act 1986. Adult male PD-APP transgenic mice and C57Bl/6NTac aged matched controls (weight range 29-45g, n1⁄4 15/group) were implanted with a telemeter i.p. and with a custom cranial implant. At seven months of age animals were evaluated in the SCORE2004 bioassay, which allows continual measurement of electro-encephalogram (EEG) and electromyogram (EMG) (cranial implant), locomotor activity and body temperature (telemetry). Animals were kept under 12/12 light/dark cycle with food and drink ad libitum. Results: At the first time point, data was compared between 10 PD-APP and 13 control animals. The time spent in REM throughout both the light and dark cycle was significantly reduced (light: PD-APP 27 6 6 minutes per 12 hour light cycle, control 476 5, P <0.05; dark: PD-APP 156 3, control 276 4, P <0.05). Additionally the average REM bout length was reduced during each light phase compared to control (light: PD-APP 0.56 0.1 minutes, control 1.06 0.1,P<0.01; dark: PD-APP 0.46 0.1, control 0.96 0.1,P<0.05). No change in the amount of time spent inNREMorwakewas observed and no significant changes in latency to NREM or REM were detected after animals were disturbed. Conclusions: In conclusion, preliminary data from this longitudinal study shows that male PD-APP mice aged 7 months have reduced time in REM and reduced average REM bout lengths in both light and dark environments. No changes in REM latency were observed in our male mice however increased latency has been reported in 3-5 month old female PDAPPmice (Huitron-Resendez et al 2002 Brain Res 928: 126-137). Evaluation of these mice, including spectral profiles, is planned to continue until animals reach 22 months of age.