Analysis of Motor Function in the Tg4-42 Mouse Model of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common form of dementia. Hallmarks of AD are memory impairments and cognitive deficits, but non-cognitive impairments, especially motor dysfunctions are also associated with the disease and may even precede classic clinical symptoms. With an aging society and increasing hospitalization of the elderly, motor deficits are of major interest to improve independent activities in daily living. Consistent with clinical findings, a variety of AD mouse models develop motor deficits as well. We investigated the motor function of 3- and 7-month-old Tg4-42 mice in comparison to wild-type controls and 5XFAD mice and discuss the results in context with several other AD mouse model. Our study shows impaired balance and motor coordination in aged Tg4-42 mice in the balance beam and rotarod test, while general locomotor activity and muscle strength is not impaired at 7 months. The cerebellum is a major player in the regulation and coordination of balance and locomotion through practice. Particularly, the rotarod test is able to detect cerebellar deficits. Furthermore, supposed cerebellar impairment was verified by 18 F-FDG PET/MRI. Aged Tg4-42 mice showed reduced cerebellar glucose metabolism in the 18 F-FDG PET. Suggesting that, deficits in coordination and balance are most likely due to cerebellar impairment. In conclusion, Tg4-42 mice develop motor deficits before memory deficits, without confounding memory test. Thus, making the Tg4-42 mouse model a good model to study the effects on cognitive decline of therapies targeting motor impairments.

Attenuation of Spatial Memory in 5xFAD Mice by Halting Cholinesterases, Oxidative Stress and Neuroinflammation Using a Cyclopentanone Derivative

“…Open field (OF), rotarod, MWM, and Y-maze tests were conducted for determining the effect of 3NCP on the behavior of the test animals in terms of locomotion, motor coordination, hippocampal-dependent spatial learning and memory, and spatial recognition memory, respectively [ 35 , 36 , 37 ].…”

Mitragyna inermis Willd (Rubiaceae) inhibits Acetylcholinesterase and Butyrylcholinesterase activities in Alzheimer’s disease mice models.

“…Alzheimer disease symptoms refer also to motor dysfunctions which can appear before classic clinical symptoms 26,27 . M. inermis may be used to protect motor memory.…”

Physical Activity Ameliorates Impaired Hippocampal Neurogenesis in the Tg4-42 Mouse Model of Alzheimer’s Disease

“…However, an analysis of the physical activity level at weeks 7 to 8 in the middle of the treatment period revealed that WT mice in general showed increased levels of physical activity compared to Tg4-42 mice. This could be likely attributed to a motor phenotype in the Tg4-42 mice, that becomes evident in tasks addressing motor coordination, such as balance beam, or in general motor performance and motor learning, which have been assessed using the rotarod task (Hüttenrauch et al., 2016a; Wagner et al., 2019). This might suggest that reduced running distance could account for the observed decrease in hippocampal neurogenesis in Tg4-42 mice.…”