Spatial learning and memory impairment and increased locomotion in a transgenic amyloid precursor protein mouse model of Alzheimer's disease

• Published in: Behavioural brain research 2011-09, Vol.222 (1), p.169-175
• Main Authors: Walker, J.M., Fowler, S.W., Miller, D.K., Sun, A.Y., Weisman, G.A., Wood, W.G., Sun, G.Y., Simonyi, A., Schachtman, T.R.
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Age Factors; Alzheimer Disease - complications; Alzheimer Disease - genetics; Alzheimer's disease; Amyloid beta-Protein Precursor - genetics; Analysis of Variance; Animals; Anxiety - diagnosis; Anxiety - etiology; Anxiety - genetics; Barnes maze; Behavioral psychophysiology; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Escape Reaction - physiology; Exploratory Behavior - physiology; Female; Fundamental and applied biological sciences. Psychology; Humans; Learning Disorders - etiology; Learning Disorders - genetics; Locomotion - genetics; Locomotion - physiology; Maze Learning - physiology; Medical sciences; Memory Disorders - etiology; Memory Disorders - genetics; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation - genetics; Neurology; Open-field; Organic mental disorders. Neuropsychology; Physical Stimulation; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Reaction Time - genetics; Retention (Psychology) - physiology; Space Perception - physiology; Spatial learning and memory; Statistics, Nonparametric; TgCRND8; Time Factors; Touch escape
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2011.03.049

► Both age groups of Tg mice showed impaired spatial learning acquisition and retention. ► Such impairment in spatial learning occurred with errors and latencies. ► Older Tg mice showed higher levels of irritability on a touch escape test. ► Both age groups of Tg mice displayed higher levels of locomotor activity. ► In sum, TgCRND8 mice show deficits in spatial and nonspatial behavioral tasks. This study provides an examination of spatial learning and a behavioral assessment of irritability and locomotion in TgCRND8 mice, an amyloid precursor protein transgenic model of Alzheimer's disease. Performance was assessed using the Barnes maze, the touch escape test, and an open-field test. While past research focused primarily on 2–5-month-old TgCRND8 mice, the present study used an older age cohort (9-month-old female mice), in addition to a 4-month-old cohort of both transgenic (Tg) and wildtype female mice. Both younger and older Tg mice displayed poor spatial learning in the Barnes maze task compared to their wildtype littermates, as demonstrated by significantly longer latencies and more errors both during acquisition and at a 2-week retest. No differences in irritability were found between Tg and control mice in the younger cohort; however, older Tg mice displayed significantly higher irritability compared with wildtype littermates, as measured by the touch escape test. Additionally, Tg mice of both age cohorts showed increased locomotion and slowed habituation during a 60-min open-field test over 3 days of testing. These results demonstrate that TgCRND8 mice show significant deficits in spatial and nonspatial behavioral tasks at advanced stages of amyloid pathology.