Zeaxanthin improved diabetes-induced anxiety and depression through inhibiting inflammation in hippocampus

Abstract

It is generally accepted that inflammation plays a key role in anxiety and depression induced by diabetes. However, the underlying mechanism and effective treatment method of these diabetes-associated behavior disorders remain to be determined. In the present study, we attempted to illuminate the implication of zeaxanthin in anxiety, depression and neuroinflammation caused by hyperglycemia, and further elaborate the relevant mechanism under these neuropsychiatric disorders. In the current work, diabetic rats were induced by high glucose and fat diet followed by a single intraperitoneal injection of streptozocin, and zeaxanthin was orally administration every day (From 6th to 19th week). Diabetes-associated anxiety and depression were assessed using open field test (OFT) and Forced swimming test (FST) respectively. Moreover, the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in hippocampus were tested using ELISA and WB. Data showed that long-term zeaxanthin treatment improve diabetic symptoms and alleviate anxiety and depression in diabetic rats. Furthermore, excessive production of IL-6, IL-1β and TNF-α could be reduced with zeaxanthin treatment. In conclusion, we suggested that zeaxanthin can ameliorate diabetes-associated anxiety and depression, inhibit inflammation in diabetic rats. Our results could provide a potential therapeutic approach for the treatment of abnormal behavior induced by hyperglycemia.

Effects of Exogenous Biliverdin Treatment on Neurobehaviors in Mice

“…High serum level of bilirubin has been found to be association with depression. 40) This confirmed that mice in the low concentration group showed depressive behaviors, while mice in the high concentration group showed anxious behaviors and decreased learning and memory ability due to nerve damage. Therefore, we hypothesized that low levels of inflammation would lead to depression in mice, while high levels of inflammation would damage neurons in mice, leading to learning and memory impairment and anxiety-like behaviors.…”

Associations between dietary carotenoid intakes and the risk of depressive symptoms

“…Beta-carotene has been shown to reduce the mRNA levels of IL-6 and TNF-α (34). Zeaxanthin can also reduce the expression of IL-6, interleukin-1β (IL-1β), and TNF-α in the hippocampus (35). Second, the development of depression is related to oxidative and an imbalance between antioxidants and prooxidants (36).…”

Prefrontal dopamine D1 receptor manipulation influences anxiety behavior and induces neuroinflammation within the hippocampus

“…But this effect is region speci c, because differences are only present in the hippocampal CA3 and DG area. Hippocampal neurons are key contributor to anxiety and depression, because either inhibition of hippocampal in ammation (Zhou et al 2018;Zhou et al 2017) as well as stimulation of BDNF expression prevented depression-like behavior (Wang et al 2016). Highlighting the key role of hippocampal functioning and mood.…”

“…An additional potential mechanism of action is enhanced hippocampal neurogenesis (Liu et al 2016). Also other manipulations can affect in ammation and induce anxiety and depression-like behavior in rodents, such as sleep deprivation (Wadhwa et al 2018;Yin et al 2017;Zielinski et al 2014), chronic mild stress (Wang et al 2018;You et al 2011) and models for chronic in ammatory disease, like diabetes or metabolic syndrome (de Cossío et al Dinel et al 2011;Zhou et al 2018). All those ndings share, that increased in ammation in the hippocampus induces anxiety and depression-like behavior in rodents, and those behavioral symptoms could be attenuated through anti-in ammatory agents which reduced among other pro-in ammatory cytokines IL-6.…”