Hydroxytyrosol alleviates oxidative stress and neuroinflammation and enhances hippocampal neurotrophic signaling to improve stress-induced depressive behaviors in mice

Author(s): Yun-Tao Zhao ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Lulu Zhang ¹ ^, ² ^, ³ ^, ⁴ , Haowen Yin ¹ ^, ² ^, ³ ^, ⁴ , Ling Shen ⁶ ^, ² ^, ³ ^, ⁴ , Wenjing Zheng ¹ ^, ² ^, ³ ^, ⁴ , Kun Zhang ¹ ^, ² ^, ³ ^, ⁴ , Jian Zeng ¹ ^, ² ^, ³ ^, ⁴ , Chuanyin Hu ⁷ ^, ⁸ ^, ³ ^, ⁴ , You Liu ¹ ^, ² ^, ³ ^, ⁴

Publication date (Electronic): 2021

Journal: Food & Function

Publisher: Royal Society of Chemistry (RSC)

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Abstract

Hydroxytyrosol exerts antidepressant-like effects in mice by reducing oxidative stress, suppressing neuroinflammation, and enhancing the function of neurotrophic factors.

Abstract

Hydroxytyrosol (HT), the main phenolic compound in olives and olive products, has antioxidative, anti-inflammatory, neuroprotective, and other physiological functions. The effects of HT on depression are unclear. The aim of this study was to explore the effects of HT on chronic unpredictable mild stress (CUMS) induced depressive-like behaviors. Mice were exposed to CUMS for 9 weeks and then treated with HT beginning in the second week and continuing for 7 weeks. Behavioral, biochemical, and molecular tests were conducted at the end of the experiment. The sucrose preference was significantly decreased in the CUMS group versus the healthy control group. Also, immobility times in forced swimming and tail suspension tests were increased in CUMS-induced mice, but treatment with HT significantly reversed this change. HT ameliorated oxidative stress in CUMS-exposed mice by enhancing superoxide dismutase activity and reducing reactive oxygen species and malondialdehyde levels in the hippocampus. HT administration significantly suppressed microglia activation and inhibited the expression of tumor necrosis factor alpha and interleukin 1 beta in the hippocampus versus the untreated group. The expression level of glial fibrillary acidic protein (GFAP) and the number of GFAP-immunoreactive astrocytes in the hippocampus were significantly augmented by HT. Furthermore, HT treatment increased the expression of hippocampal brain-derived neurotrophic factor (BDNF), phosphorylated tropomyosin receptor kinase B (p-TrkB), and phosphorylated c-AMP response element binding protein (p-CREB) compared with the untreated CUMS group. Overall, HT improved CUMS-induced depressive-like behaviors in mice by alleviating oxidative stress and neuroinflammation and by enhancing the BDNF/TrkB/CREB signaling pathway.

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Aaron Kandola, Garcia Ashdown-Franks, Joshua Hendrikse … (2019)

Physical activity can treat and prevent depressive symptoms, but its antidepressant mechanisms are yet to be established. In this review, we comprehensively assess key biological and psychosocial mechanisms through which physical activity exerts antidepressant effects, with a particular focus on exercise. Exercise, a subset of physical activity, influences a range of biological and psychosocial processes also implicated in the pathophysiology of depression. We focus on the capacity for exercise to elicit changes in neuroplasticity, inflammation, oxidative stress, the endocrine system, self-esteem, social support and self-efficacy. We also discuss how a better understanding of these mechanisms can inform the way we design and implement exercise-based interventions to maximise their antidepressant effects on an individual basis. We conclude by presenting a conceptual framework of the key biological and psychosocial mechanisms underlying the relationship between physical activity and depressive symptoms, and the moderators and confounders that may influence it.