Amide Proton Transfer-Weighted Imaging Detects Hippocampal Proteostasis Disturbance Induced by Sleep Deprivation at 7.0 T MRI

Sleep deprivation leads to hippocampal injury. Proteostasis disturbance is an important mechanism linking sleep deprivation and hippocampal injury. However, identifying noninvasive imaging biomarkers for hippocampal proteostasis disturbance remains challenging. Amide proton transfer-weighted (APTw) imaging is a chemical exchange saturation transfer technique based on the amide protons in proteins and peptides. We aimed to explore the ability of APTw imaging in detecting sleep deprivation-induced hippocampal proteostasis disturbance and its biological significance, as well as its biological basis. In vitro, the feasibility of APTw imaging in detecting changes of the protein state was evaluated, demonstrating that APTw imaging can detect alterations in the protein concentration, conformation, and aggregation state. In vivo, the hippocampal APTw signal declined with increased sleep deprivation time and was significantly lower in sleep-deprived rats than that in normal rats. This signal was positively correlated with the number of surviving neurons counted in Nissl staining and negatively correlated with the expression of glucose-regulated protein 78 evaluated in immunohistochemistry. Differentially expressed proteins in proteostasis network pathways were identified in the hippocampi of normal rats and sleep-deprived rats via mass spectrometry proteomics analysis, providing the biological basis for the change of the hippocampal APTw signal in sleep-deprived rats. These findings demonstrate that APTw imaging can detect hippocampal proteostasis disturbance induced by sleep deprivation and reflect the extent of neuronal injury and endoplasmic reticulum stress.