Amyloid-β (Aβ) and Aβ plaques can disrupt synaptic plasticity, leading to abnormalities in sensory function and cognition in Alzheimer's disease (AD). The whisker sensorimotor system is crucial for tactile perception, providing rodents with spatial and textural features information about their surroundings. Sensory inputs from whiskers have a clear topological localization in the barrel cortex.
Objective
Previous studies have suggested that sensory stimulation can effectively ameliorate the pathology of AD mice and improve cognitive performance. However, it remains unknown whether tactile stimulation via whiskers can activate cortical sensory areas, protect synaptic structure and function.
Methods
Here, we established a whisker deprivation (WD) model in the 5×FAD mouse.
Results
We found that WD aggravated the deposition of Aβ1−42, 6E10 and fibrotic Aβ in the cortex, hippocampus and thalamus. Simultaneously, changes in dendritic morphology were consistent with the decreased pCreb levels in the hippocampal dentate gyrus region. WD also reduced axonal projections from layer L4/L5a to L2/3 in the barrel cortex, as well as projections from the entorhinal cortex to the DG, which may disrupt the integration of information in cortical functional columns and weaken the efficiency of information transmission. Additionally, we observed sex differences in effects of WD on AD pathology in 5×FAD mice, with female mice being more sensitive to WD treatment. Ultimately, WD impaired working memory, spatial memory and social behavior in 5×FAD mice.
Conclusions
Our study suggested that WD exacerbated the progression of AD pathology in 5×FAD mice, which implicated with Aβ aggravation and synaptic dysfunction.
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