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Ongoing Electroencephalographic Activity Associated with Cortical Arousal in Transgenic PDAPP Mice (hAPP V717F)

[ Vol. 15 , Issue. 3 ]

Author(s):

Claudio Del Percio, Wilhelmus Drinkenburg, Susanna Lopez, Cristina Limatola, Jesper F. Bastlund, Ditte Z. Christensen, Jan T. Pedersen, Gianluigi Forloni, Angelisa Frasca, Francesco M. Noe, Marina Bentivoglio, Paolo F. Fabene, Giuseppe Bertini, Valeria Colavito, Sophie Dix, Raffaele Ferri, Regis Bordet, Jill C. Richardson and Claudio Babiloni*   Pages 259 - 272 ( 14 )

Abstract:


Background: It has been shown that theta (6-10 Hz) and delta (1-6 Hz) ongoing electroencephalographic (EEG) rhythms revealed variations in the cortical arousal in C57 Wild Type (WT) mice during cage exploration (active condition) compared to awake quiet behavior (passive condition; IMI PharmaCog project, www.pharmacog.eu).

Objective: The objective was to test if these EEG rhythms might be abnormal in old PDAPP mice modeling Alzheimer's disease (AD) with a hAPP Indiana V717F mutation (They show abnormal neural transmission, cognitive deficits, and brain accumulation of Aβ1-42).

Methods: Ongoing EEG rhythms were recorded by a frontoparietal bipolar channel in 15 PDAPP and 23 WT C57 male mice (mean age of 22.8 months ±0.4 and 0.3 standard error, respectively). EEG absolute power (density) was calculated. Frequency and amplitude of individual delta and theta frequency (IDF and ITF) peaks were considered during passive and active states in the wakefulness.

Results: Compared with the WT group, the PDAPP group showed higher frequency of the IDF during the passive condition and lower frequency of the ITF during the active state. Furthermore, the WT but not PDAPP group showed significant changes in the frontoparietal EEG power (IDF, ITF) during active over passive state.

Conclusion: PDAPP mice were characterized by less changes in the brain arousal during an active state as revealed by frontoparietal EEG rhythms. Future studies will have to cross-validate the present results on large animal groups, clarify the neurophysiological underpinning of the effect, and test if the disease modifying drugs against AD amyloidosis normalize those candiate EEG biomarkers in PDAPP mice

Keywords:

Electroencephalography (EEG), Alzheimer's disease (AD), PDAPP mice, awake active state, awake passive state, cortical arousal.

Affiliation:

IRCCS SDN, Naples, Janssen Research and Development, Pharmaceutical Companies of J&J, Turnhoutseweg 30, Beerse, Department of Physiology and Pharmacology, University of Rome “La Sapienza”, Rome, Department of Physiology and Pharmacology, University of Rome “La Sapienza”, Rome, H. Lundbeck A/S, Ottiliavej 9, DK-2500, Valby, H. Lundbeck A/S, Ottiliavej 9, DK-2500, Valby, H. Lundbeck A/S, Ottiliavej 9, DK-2500, Valby, Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Department of Neurological Biomedical and Movement Sciences, University of Verona, Verona, Department of Neurological Biomedical and Movement Sciences, University of Verona, Verona, Department of Neurological Biomedical and Movement Sciences, University of Verona, Verona, Department of Neurological Biomedical and Movement Sciences, University of Verona, Verona, Eli Lilly, Erl Wood Manor, Windlesham, Surrey, Department of Neurology, IRCCS Oasi Institute for Research on Mental Retardation and Brain Aging, Troina (EN), Department of Medical Pharmacology, University Lille -2 Nord de France, Lille, GlaxoSmithKline R&D Neurotherapeutics Area UK, Gunnels Wood Road, Stevenage, Hertfordshire, IRCCS San Raffaele Pisana, Rome



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