Selective TRPC6 Modulator, C20, Improves Cognitive but Not Motor Function in a 5xFAD Mouse Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is characterized by progressive neurodegeneration, synaptic dysfunction, and cognitive impairment. In this study, we examined the effects of compound C20, a selective positive allosteric modulator of the TRPC6 channel, on the cognitive and motor function of 5xFAD mice, a transgenic model of AD. Our results demonstrate that C20 effectively improves hippocampus-dependent (“Morris’s water maze”, “Novel object recognition” tests) and hippocampus-independent (“Fear conditioning”) memory, which is consistent with its ability to restore synaptic plasticity. However, C20 had no effect on motor impairment in the “Beam walking” test. Thus, C20 exhibits an effect of protection of cognition but does not affect motor function in 5xFAD mice. These findings support the potential of TRPC6 as a target for the treatment of cognitive impairment in a course of AD and highlight the need for further investigation of the mechanisms underlying motor deficits.