Modulation of the neurotransmitter systems through the anti-inflammatory and antidepressant-like effects of squalene from Aurantiochytrium sp.

Abstract

Although algae have been the focal point of biofuel research, studies on their biological activities have been limited. In recent years, however, the importance of algae as sources of functional ingredients has been recognized due to their health beneficial effects. In this study, we evaluated the antidepressant-like activities of ethanol extract of Aurantiochytrium sp. (EEA) in the forced swimming test (FST)-induced depression in ICR mice. Imipramine, a commercially available tricyclic antidepressant drug, was used as positive control. Animals were administered EEA orally for 14 consecutive days and were subjected to the locomotor activity testing. Additionally, changes in gene expression in mice brain were assessed by real-time PCR and microarray assays to understand the molecular mechanisms underlying the effect of EEA. We found that the immobility time in FST was significantly reduced in the EEA-treated mice compared to that of in the control mice. Microarray and real-time PCR results revealed that EEA treatment induced changes in several genes in mice brain associated with pro-inflammation and dopaminergic, cholinergic, glutamatergic, and serotonergic synapses. It has previously been reported that several cytokines, such as IL-6 and TNF-α, which mediate neuroinflammation, are also responsible for indirectly altering brain neurotransmitter levels in neuropsychiatric disorders. Therefore, the regulation of the expression of pro-inflammatory genes in EEA-administered mice brain is considered to contribute to the enhancement of neurotransmitter systems-related gene expression in our study. Moreover, our in vitro study suggested that squalene, a component produced by Aurantiochytrium , was one of the active substances in EEA. In conclusion, our study provides the first evidence that Aurantiochytrium sp. can reduce neuroinflammation that may contribute to the modulation of the neurotransmitter systems, which could underlie its antistress and antidepressant effects.

Microalgae Aurantiochytrium Sp. Increases Neurogenesis and Improves Spatial Learning and Memory in Senescence-Accelerated Mouse-Prone 8 Mice

“…In our previous study, we orally administered 100 mg/kg of EEA for 14 consecutive days to depression model mice to evaluate its antidepressant-like activities (Sasaki et al, 2019a ). Considering this previous study, 50 mg/kg was determined as the concentration for oral administration of EEA and HEEA.…”

“…(EEA) had anti-inflammatory effects on RAW264.7 cells (Takahashi et al, 2018 ). Moreover, EEA also showed an antidepressant-like effect via anti-inflammation (Sasaki et al, 2019a ). However, the effects of Aurantiochytrium sp.…”

The Microalgae Aurantiochytrium Sp. Increases Neurogenesis and Improves Spatial Learning and Memory in Senescence-Accelerated Prone 8 Mice

“…These results suggest that HEEA can induce differentiation of NPC into both neurons or glia while EEA keeps them in an undifferentiated state. Recent studies showed EEA and one of its active components, squalene, have neuroprotective effects, protecting stressed neurons from cell death [10]. Several genes related to chemokine signaling pathways are downregulated in EEA-treated mice and may contribute to anti-in ammatory effects [10].…”

“…Recent studies showed EEA and one of its active components, squalene, have neuroprotective effects, protecting stressed neurons from cell death [10]. Several genes related to chemokine signaling pathways are downregulated in EEA-treated mice and may contribute to anti-in ammatory effects [10]. Squalene, which is concentrated in the HEEA layer, is essential in NSCs and NPC cholesterol biosynthesis.…”

“…However, recent studies demonstrated that an ethanol extract obtained from Aurantiochytrium sp (EEA) had anti-in ammatory effects on RAW264.7 cells [9]. Moreover, EEA also showed an anti-depressant-like effect via anti-in ammation [10]. However, the effects of Aurantiochytrium sp.…”