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Steroid sulfatase inhibitor DU-14 prevents amyloid β-protein-induced depressive-like behavior and theta rhythm suppression in rats

YUE Xing-Hua^1,*, WANG Zhao-Jun², WU Mei-Na², CAI Hong-Yan³, ZHANG Jun²

¹First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300193, China；²Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China；³Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan 030001, China

Abstract

The hippocampus, a major component of the limbic system, is the most important region related to emotion regulation and memory processing. Cognitive impairment and depressive symptoms observed in Alzheimer's disease (AD) patients may be attributed to hippocampal damage caused by amyloid β-protein (Aβ). Our previous studies have demonstrated that a steroid sulfatase inhibitor DU-14 can enhance hippocampal synaptic plasticity and spatial memory abilities in a chronic AD murine model by counteracting the toxic effects of Aβ. However, limited experimental evidence exists regarding the efficacy of steroid sulfatase inhibitor on depressive symptoms in AD animal models. In this study, we investigated the effects of DU-14 on depressive symptoms and theta-band neuronal oscillations in rats with intrahippocampal injection of Aβ1-42 using various behavioral tests such as sucrose preference test, tail suspension test, forced swimming test, and in vivo hippocampal local field potential (LFP) recording. The results demonstrated that, in comparison to the control group: (1) rats in the Aβ group exhibited a decrease in sucrose preference, indicating a loss of interest in pleasurable activities; (2) rats in the Aβ group displayed aggravated depressive-like behavior characterized by prolonged immobility time during tail suspension and forced swimming tests; (3) Aβ disrupted the induction of theta rhythm via tail pinch stimulation, and resulted in a significant reduction in peak power of theta rhythm. In contrast to the Aβ group, pretreatment with DU-14 resulted in: (1) a significant improvement in Aβ-induced anhedonia, as evidenced by increased sucrose preference; (2) significant alleviation of Aβ-induced despair and depressive-like behaviors, reflected by reduced immobility time during tail suspension and forced swimming tests; (3) successful mitigation of Aβ-mediated inhibition on bilateral hippocampal theta rhythm. These findings indicate that steroid sulfatase inhibitor DU-14 can counteract neurotoxicity induced by Aβ, and prevent Aβ-induced depressive-like behavior and suppression of theta rhythm.

Key words: amyloid β-protein; steroid sulfatase inhibitor; depression; Alzheimer''s disease; theta rhythm

Received: 　　Accepted:

Corresponding author: 岳兴华　　E-mail:

DOI: 10.13294/j.aps.2025.0052

Citing This Article：

YUE Xing-Hua, WANG Zhao-Jun, WU Mei-Na, CAI Hong-Yan, ZHANG Jun. Steroid sulfatase inhibitor DU-14 prevents amyloid β-protein-induced depressive-like behavior and theta rhythm suppression in rats. Acta Physiol Sin 2025; 77 (5): 801-810 (in Chinese with English abstract).