Hyperactivity with Agitative-Like Behavior in a Mouse Tauopathy Model

• Published in: Journal of Alzheimer's disease Vol. 49; no. 3; p. 783
• Main Authors: Jul, Pia, Volbracht, Christiane, de Jong, Inge E M, Helboe, Lone, Elvang, Anders Brandt, Pedersen, Jan Torleif
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2016
• Subjects: Age Factors; Analysis of Variance; Animals; Brain - drug effects; Brain - metabolism; Cognition Disorders - etiology; Disease Models, Animal; Doxycycline - therapeutic use; Exploratory Behavior - drug effects; Humans; Hyperkinesis - etiology; Hyperkinesis - prevention & control; Male; Maze Learning - drug effects; Mice; Mice, Transgenic; Motor Activity - drug effects; Motor Activity - genetics; Mutation - genetics; Psychomotor Agitation - etiology; Psychomotor Agitation - prevention & control; tau Proteins - genetics; Tauopathies - complications; Tauopathies - genetics; Tauopathies - pathology; Time Factors; frontotemporal dementia; Agitation; Alzheimer’s disease; hyperactivity; rTg4510; P301L
• ISSN: 1875-8908
• DOI: 10.3233/JAD-150292

Tauopathies, such as Alzheimer's disease (AD) and frontotemporal dementia (FTD), are characterized by formation of neurofibrillary tangles consisting of hyperphosphorylated tau. In addition to memory loss, patients experience behavioral symptoms such as agitation, aggression, depression, and insomnia. We explored the behavioral phenotype of a mouse model (rTg4510) carrying the human tau P301L mutation found in a familial form of FTD. We tested these mice in locomotor activity assays as well as in the Morris water maze to access spatial memory. In addition to cognitive impairments, rTg4510 mice exhibited a hyperactivity phenotype which correlated with progression of tau pathology and was dependent on P301L tau transgene expression. The hyperactive phenotype was characterized by significantly increased locomotor activity in a novel and in a simulated home cage environment together with a disturbed day/night cycle. The P301L-tau-dependent hyperactivity and agitative-like phenotype suggests that these mice may form a correlate to some of the behavioral disturbances observed in advanced AD and FTD.