Lu Jiashu, Huang Chao, Lu Qun, Lu Xu
Department of Pharmacy, The People's Hospital of Taizhou, The Fifth Affiliated Hospital of Nantong University, Taizhou, China.
Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, China.
Front Pharmacol. 2022 Jul 15;13:918177. doi: 10.3389/fphar.2022.918177. eCollection 2022.
Recently, innate immune system stimulants, such as lipopolysaccharide (LPS) and macrophage-colony stimulating factor (M-CSF), were reported to prevent and reverse chronic stress-induced behavioral abnormalities, suggesting that innate immune stimulation could be a potential strategy for the treatment and prevention of mental disorders. Amphotericin B liposome is a clinically available antifungal medication that can stimulate macrophages and microglia. We hypothesize that amphotericin B liposome may be used to prevent and reverse behavioral abnormalities triggered by chronic stress. As expected, our results showed that a single injection of amphotericin B liposome (1 mg/kg) immediately after stress cessation reversed the decrease in time spent in the interaction zone in the social interaction test (SIT) and the increase in immobility time in the tail suspension test (TST) and forced swimming test (FST) in mice caused by chronic social defeat stress (CSDS). In addition, a single injection of amphotericin B liposomes (1 mg/kg) 1 day before stress exposure was found to prevent the CSDS-induced decrease in time spent in the interaction zone in the SIT and the increase in immobility time in the TST and FST in mice. Pretreatment with minocycline to inhibit the innate immune response was able to abolish the reversal effect of post-stress injection of amphotericin B liposomes on CSDS-induced behavioral abnormalities and the prophylactic effect of pre-stress injection of amphotericin B liposomes on CSDS-induced behavioral abnormalities. These results demonstrate that amphotericin B liposomes have both therapeutic and prophylactic effects on chronic stress-induced behavioral abnormalities in mice by mobilizing the innate immune response.
最近，有报道称，诸如脂多糖（LPS）和巨噬细胞集落刺激因子（M-CSF）等先天免疫系统刺激剂可预防和逆转慢性应激诱导的行为异常，这表明先天免疫刺激可能是治疗和预防精神障碍的一种潜在策略。两性霉素B脂质体是一种临床可用的抗真菌药物，可刺激巨噬细胞和小胶质细胞。我们假设两性霉素B脂质体可用于预防和逆转慢性应激引发的行为异常。正如预期的那样，我们的结果表明，在应激停止后立即单次注射两性霉素B脂质体（1毫克/千克）可逆转慢性社会挫败应激（CSDS）导致的小鼠社会互动测试（SIT）中在互动区停留时间的减少以及悬尾测试（TST）和强迫游泳测试（FST）中不动时间的增加。此外，发现在应激暴露前1天单次注射两性霉素B脂质体（1毫克/千克）可预防CSDS诱导的小鼠SIT中在互动区停留时间的减少以及TST和FST中不动时间的增加。用米诺环素预处理以抑制先天免疫反应能够消除应激后注射两性霉素B脂质体对CSDS诱导的行为异常的逆转作用以及应激前注射两性霉素B脂质体对CSDS诱导的行为异常的预防作用。这些结果表明，两性霉素B脂质体通过调动先天免疫反应对小鼠慢性应激诱导的行为异常具有治疗和预防作用。
