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Identification of a Microglial Activation-Dependent Antidepressant Effect of Amphotericin B Liposome

Identification of a Microglial Activation-Dependent Antidepressant Effect of Amphotericin B Liposome

Minhui Gao, Peili Hu, Zixuan Cai, Yue Wu, Dan Wang, Wenfeng Hu, Xing Xu, Yaru Zhang, Xu Lu, Dongjian Chen, Zhuo Chen, Kai Ma, Jie Wen, Hui Wang, Chao Huang

Neuropharmacology. 2019 Jun;151:33-44.

PMID: 30954529

Abstract:

Chronic stress-induced decline in microglia in the hippocampus is a newly hypothesized mechanism of depression, and reversal of this decline by microglial activators has been shown to suppress depression-like behaviors in mice. This suggests that activation of immune cells in the hippocampus may be a potential strategy for depression therapy. Since amphotericin B, an anti-fungal medication, is known to activate macrophages and microglia, we investigated whether conventional amphotericin B or its liposomal form displays antidepressant activity. Our results showed that both amphotericin B and its liposomal form at various doses induced obvious depression-like behaviors in naïve mice, likely owing to increased serum interleukin-6 (IL-6) and IL-1β levels. However, under stressed conditions, amphotericin B liposome, but not amphotericin B itself, reversed chronic unpredictable stress (CUS)-induced increase in immobility time in the tail suspension test and forced swim test as well as CUS-induced decrease in sucrose intake in the sucrose preference test and the time spent in the center region of the open field test in a dose-dependent manner. Immunofluorescence analysis showed that amphotericin B liposome reversed the CUS-induced decline in dentate gyrus (DG) microglia, and inhibition or ablation of microglia in the hippocampus by minocycline (40 mg/kg) or PLX3397 pre-treatment (290 mg/kg) abrogated the antidepressant effect of the amphotericin B liposome in CUS-treated mice. These results not only identify a novel pharmacological effect of amphotericin B liposome, but further support the notion that microglial activation in the hippocampus is a potential strategy for depression therapy.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1397893-A	Amphotericin B		1397-89-3	Price

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