Simvastatin therapy in adolescent mice attenuates HFD-induced depression-like behavior by reducing hippocampal neuroinflammation.


State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 211198, China; School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China; Qinghai Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, Qinghai Province, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [Email]


A high-fat diet (HFD)-induced obesity/hyperlipidemia is accompanied by hormonal and neurochemical changes that can be associated with depression. Emerging studies indicate that simvastatin (SMV, decreasing cholesterol levels) has therapeutic effects on neurological and neuropsychiatric diseases through hippocampal-dependent function. However, the studies on the HFD exposure in adolescent animals, which investigate the neuroprotective effects of SMV on the hippocampal morphology, serotonin (5-HT) system and inflammation, are limited. Hence, the aim of this study was to determine whether SMV attenuates HFD-induced major depressive disorders in adolescent animals and, more specifically, acts as an anti-neuroinflammatory response.