Altered theta oscillations and aberrant cortical excitatory activity in the 5XFAD model of Alzheimer's disease.
Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by impairment of memory function. The 5XFAD mouse model was analyzed and compared with wild-type (WT) controls for aberrant cortical excitability and hippocampal theta oscillations by using simultaneous video-electroencephalogram (EEG) monitoring. Seizure staging revealed that 5XFAD mice exhibited cortical hyperexcitability whereas controls did not. In addition, 5XFAD mice displayed a significant increase in hippocampal theta activity from the light to dark phase during nonmotor activity. We also observed a reduction in mean theta frequency in 5XFAD mice compared to controls that was again most prominent during nonmotor activity. Transcriptome analysis of hippocampal probes and subsequent qPCR validation revealed an upregulation of Plcd4 that might be indicative of enhanced muscarinic signalling. Our results suggest that 5XFAD mice exhibit altered cortical excitability, hippocampal dysrhythmicity, and potential changes in muscarinic signaling.
Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany.
Magdalena Elisabeth
ME
Siwek
Department of Psychiatry and Psychotherapy, University of Cologne, Faculty of Medicine, Kerpener Street 62, 50937 Cologne, Germany.
Ralf
R
Müller
Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany.
Christina
C
Henseler
Institute of Molecular Psychiatry, University of Bonn, Sigmund-Freud Street 25, 53125 Bonn, Germany.
Astrid
A
Trog
Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany.
Andreas
A
Lundt
Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany.
Carola
C
Wormuth
Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany.
Karl
K
Broich
German Center for Neurodegenerative Diseases (DZNE), Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
Dan
0000-0001-7464-1335
D
Ehninger
Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany.
Marco
M
Weiergräber
Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany.
Anna
A
Papazoglou
D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002540:Cerebral Cortex / Q000503:physiopathology*; D004195:Disease Models, Animal; D004569:Electroencephalography; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D053764:Presenilin-1 / Q000235:genetics; D012640:Seizures / Q000503:physiopathology*; D013826:Theta Rhythm
D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1