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Sci Rep ; 9(1): 4512, 2019 03 14.
Article in English | MEDLINE | ID: mdl-30872728

ABSTRACT

Sleep deprivation (SD) is the hallmark of modern society and may increase risk of Alzheimer's disease (AD). However, it is unclear how SD facilitates early cognitive impairments observed in AD models, as the underlying molecular mechanism is largely unknown. Here, we aim to investigate SD-induced cellular and molecular alterations in hippocampus of young APP/PS1 mice and whether jujuboside A (JuA) treatment could negate these alterations. Our results reveal that although SD causes spatial memory impairments in both genotypes, SD decreases frequency and amplitude of mEPSCs and pCREB levels in WT, but increases frequency and amplitude of mEPSCs, NMDAR, GluR1, pCaMKII (ß, α) and decreases CREB levels in APP/PS1 mice, implicating that SD may facilitate abnormalities in young APP/PS1 mice via enhancing neuronal excitability. Moreover, JuA suppresses SD-induced enhancement of mEPSCs and prevents memory impairment in APP/PS1 mice. Further, whole-cell puff experiment suggests that JuA may function to activate GABAergic inhibition to reduce SD-induced enhancement of excitatory synaptic transmission in APP/PS1 mice. The present study reveals that sleep loss induces spatial memory impairment in an AD mouse model by disrupting the excitatory signaling pathway, and JuA prevents this via GABAergic mechanism.


Subject(s)
Amyloid beta-Protein Precursor/genetics , Hippocampus/drug effects , Memory Disorders/prevention & control , Neuroprotective Agents/administration & dosage , Saponins/administration & dosage , Sleep Wake Disorders/drug therapy , Animals , Cyclic AMP Response Element-Binding Protein/metabolism , Disease Models, Animal , Female , Hippocampus/physiopathology , Male , Maze Learning/drug effects , Memory Disorders/genetics , Memory Disorders/metabolism , Mice , Mice, Transgenic , Neurons/drug effects , Neurons/physiology , Neuroprotective Agents/pharmacology , Saponins/pharmacology , Sleep Wake Disorders/genetics , Sleep Wake Disorders/metabolism
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