Ongoing Electroencephalographic Rhythms Related to Exploratory Movements in Transgenic TASTPM Mice

Author:

Del Percio Claudio1,Drinkenburg Wilhelmus2,Lopez Susanna13,Pascarelli Maria Teresa4,Lizio Roberta5,Noce Giuseppe5,Ferri Raffaele4,Bastlund Jesper Frank6,Laursen Bettina6,Christensen Ditte Zerlang6,Pedersen Jan T.6,Forloni Gianluigi7,Frasca Angelisa7,Noè Francesco M.7,Fabene Paolo Francesco8,Bertini Giuseppe8,Colavito Valeria8,Bentivoglio Marina8,Kelley Jonathan2,Dix Sophie9,Infarinato Francesco10,Soricelli Andrea511,Stocchi Fabrizio12,Richardson Jill C.13,Babiloni Claudio114,

Affiliation:

1. Department of Physiology and Pharmacology “V Erspamer”, Sapienza University of Rome, Rome, Italy

2. Janssen Research and Development, Pharmaceutical Companies of J&J, Beerse, Belgium

3. Department of Emergency and Organ Transplantation - Nephrology, Dialysis and Transplantation Unit, Aldo Moro University of Bari, Bari, Italy

4. Oasi Research Institute - IRCCS, Troina, Italy

5. IRCCS SDN, Naples, Italy

6. H. Lundbeck A/S, Valby, Denmark

7. Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy

8. Department of Neurological Biomedical and Movement Sciences, University of Verona, Verona, Italy

9. Eli Lilly, Erl Wood Manor, Windlesham, Surrey, UK

10. IRCCS San Raffaele Pisana, Rome, Italy

11. Department of Motor Sciences and Healthiness, University of Naples Parthenope, Naples, Italy

12. Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Roma, Italy

13. GlaxoSmithKline R&D Neurotherapeutics Area UK, Gunnels Wood Road, Stevenage, Hertfordshire, UK

14. San Raffaele Cassino, Cassino (FR), Italy

Abstract

Background: The European PharmaCog study (http://www.pharmacog.org) has reported a reduction in delta (1–6 Hz) electroencephalographic (EEG) power (density) during cage exploration (active condition) compared with quiet wakefulness (passive condition) in PDAPP mice (hAPP Indiana V717F mutation) modeling Alzheimer’s disease (AD) amyloidosis and cognitive deficits. Objective: Here, we tested the reproducibility of that evidence in TASTPM mice (double mutation in APP KM670/671NL and PSEN1 M146V), which develop brain amyloidosis and cognitive deficits over aging. The reliability of that evidence was examined in four research centers of the PharmaCog study. Methods: Ongoing EEG rhythms were recorded from a frontoparietal bipolar channel in 29 TASTPM and 58 matched “wild type” C57 mice (range of age: 12–24 months). Normalized EEG power was calculated. Frequency and amplitude of individual delta and theta frequency (IDF and ITF) peaks were considered during the passive and active conditions. Results: Compared with the “wild type” group, the TASTPM group showed a significantly lower reduction in IDF power during the active over the passive condition (p < 0.05). This effect was observed in 3 out of 4 EEG recording units. Conclusion: TASTPM mice were characterized by “poor reactivity” of delta EEG rhythms during the cage exploration in line with previous evidence in PDAPP mice. The reliability of that result across the centers was moderate, thus unveiling pros and cons of multicenter preclinical EEG trials in TASTPM mice useful for planning future studies.

Publisher

IOS Press

Subject

Psychiatry and Mental health,Geriatrics and Gerontology,Clinical Psychology,General Medicine,General Neuroscience

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