[Wuyou Decoction alleviates hippocampal neuronal injury and improves synaptic plasticity in rats with chronic sleep deprivation by inhibiting ferroptosis via activating the Nrf2/HO-1 pathway].

Abstract

Objectives: To investigate the mechanism of Wuyou Decoction (WYD) for ameliorating hippocampal neuron damage and protecting synaptic plasticity in rats with chronic sleep deprivation (CSD).

Methods: Fifty SD rats were randomly divided into normal control group, CSD model group, and low-, medium-, and high-dose WYD treatment groups (n=10). Except for those in the control group, all the rats were subjected to CSD modeling using the horizontal platform method. Cognitive function of the rats was assessed with Morris water mazetest, and hippocampal pathology, synaptic structure, iron content, oxidative stress markers, and ferroptosis-related protein expressions were evaluated. Molecular docking study was performed to explore the interactions between WYD components and ferroptosis-related proteins.

Results: CSD induced significant cognitive impairment and neuronal and synaptic damage in the rat models, causing also increased oxidative stress and iron deposition and upregulated Nrf2 and HO-1 expressions. Treatment with WYD, especially at the medium dose, significantly improved learning and memory abilities of the rat models, alleviated neuronal degeneration, restored synaptic structure, reduced iron accumulation and oxidative stress, and upregulated ferroptosis-related markers as well as Nrf2 and HO-1 expressions.

Conclusions: WYD, optimally at the medium dose, alleviates CSD-induced cognitive impairment in rats by inhibiting ferroptosis, reducing neuronal damage, and enhancing synaptic repair via activation of the Nrf2/HO-1 signaling pathway.