Ongoing Electroencephalographic Rhythms Related to Exploratory Movements in Transgenic TASTPM Mice

Article type: Research Article

Authors: Del Percio, Claudio^a | Drinkenburg, Wilhelmus^b | Lopez, Susanna^{a; c} | Pascarelli, Maria Teresa^d | Lizio, Roberta^e | Noce, Giuseppe^e | Ferri, Raffaele^d | Bastlund, Jesper Frank^f | Laursen, Bettina^f | Christensen, Ditte Zerlang^f | Pedersen, Jan T.^f | Forloni, Gianluigi^g | Frasca, Angelisa^g | Noè, Francesco M.^g | Fabene, Paolo Francesco^h | Bertini, Giuseppe^h | Colavito, Valeria^h | Bentivoglio, Marina^h | Kelley, Jonathan^b | Dix, Sophieⁱ | Infarinato, Francesco^j | Soricelli, Andrea^{e; k} | Stocchi, Fabrizio^l | Richardson, Jill C.^m | Babiloni, Claudio^{a; n; *} | on behalf of PharmaCog Consortium

Affiliations: [a] Department of Physiology and Pharmacology “V Erspamer”, Sapienza University of Rome, Rome, Italy | [b] Janssen Research and Development, Pharmaceutical Companies of J&J, Beerse, Belgium | [c] Department of Emergency and Organ Transplantation - Nephrology, Dialysis and Transplantation Unit, Aldo Moro University of Bari, Bari, Italy | [d] Oasi Research Institute - IRCCS, Troina, Italy | [e] IRCCS SDN, Naples, Italy | [f] H. Lundbeck A/S, Valby, Denmark | [g] Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy | [h] Department of Neurological Biomedical and Movement Sciences, University of Verona, Verona, Italy | [i] Eli Lilly, Erl Wood Manor, Windlesham, Surrey, UK | [j] IRCCS San Raffaele Pisana, Rome, Italy | [k] Department of Motor Sciences and Healthiness, University of Naples Parthenope, Naples, Italy | [l] Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Roma, Italy | [m] GlaxoSmithKline R&D Neurotherapeutics Area UK, Gunnels Wood Road, Stevenage, Hertfordshire, UK | [n] San Raffaele Cassino, Cassino (FR), Italy

Correspondence: [*] Correspondence to: Prof. Claudio Babiloni, PhD, Department of Physiology and Pharmacology “V Erspamer”, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy. Tel./Fax: +39 06 49910989 0917; E-mail: [email protected].

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.

Keywords: Active and passive state in wakefulness, Alzheimer’s disease, electroencephalography, TASTPM mice, wild type mice

DOI: 10.3233/JAD-190351

Journal: Journal of Alzheimer's Disease, vol. 78, no. 1, pp. 291-308, 2020