Gastrodin attenuates high fructose-induced sweet taste preference decrease by inhibiting hippocampal neural stem cell ferroptosis.

INTRODUCTION: High fructose intake has been implicated as a risk factor for behavioral disorders, potentially through cell ferroptosis induction in the central nervous system. Neural stem cells (NSCs) are crucial for maintaining hippocampal neurogenesis to resist behavioral alterations. Gastrodin, derived from the traditional Chinese herb Gastrodia elata, has neuroprotective effect. OBJECTIVES: This study aimed to elucidate the underlying mechanism by which high fructose induces sweet taste preference and assesses the impact of gastrodin on hippocampal NSC ferroptosis. METHODS: Mice and cultured NSCs were treated with high fructose and/or gastrodin, respectively. NSC ferroptosis was evaluated by assay of lipid peroxidation and DNA double-strand breaks. Transcriptome sequencing (RNA-seq), Western blotting, and chromatin immunoprecipitation (ChIP) were employed to explore the potential mechanism underlying high fructose-induced NSC ferroptosis and the modulation of gastrodin. Simultaneously, specific gene expression was regulated by lentivirus injection into the hippocampus of mice. RESULTS: Our data showed that gastrodin mitigated sweet taste preference decline and hippocampal NSC ferroptosis in high fructose-fed mice, being consistent with reduction of reactive oxygen species (ROS) and iron accumulation in hippocampal NSC mitochondria. Mechanistically, we identified CDGSH iron-sulfur domain 1 (CISD1) as a mediator of NSC ferroptosis, with its expression being augmented by high fructose. Overexpression of Zic family member 2 (ZIC2) increased the transcription of Cisd1 gene. Additionally, overexpression of Zic2 with lentiviral vectors in hippocampus showed the decreased sweet taste preference in mice, consistently up-regulated CISD1 protein expression and reduced hippocampal NSC number. Gastrodin downregulated ZIC2 expression to inhibit CISD1 transcription in its attenuation of high fructose-induced NSC ferroptosis and sweet taste preference decrease. CONCLUSION: Collectively, high fructose can drive hippocampal NSC ferroptosis by upregulating ZIC2 and CISD1 expression, thereby contributing to the decline in sweet taste preference. Gastrodin emerges as a promising agent for mitigating NSC ferroptosis and improving sweet taste preference.

Short-Chain Fatty Acids Ameliorate Depressive-like Behaviors of High Fructose-Fed Mice by Rescuing Hippocampal Neurogenesis Decline and Blood-Brain Barrier Damage.

Excessive fructose intake is associated with the increased risk of mental illness, such as depression, but the underlying mechanisms are poorly understood. Our previous study found that high fructose diet (FruD)-fed mice exhibited neuroinflammation, hippocampal neurogenesis decline and blood-brain barrier (BBB) damage, accompanied by the reduction of gut microbiome-derived short-chain fatty acids (SCFAs). Here, we found that chronic stress aggravated these pathological changes and promoted the development of depressive-like behaviors in FruD mice. In detail, the decreased number of newborn neurons, mature neurons and neural stem cells (NSCs) in the hippocampus of FruD mice was worsened by chronic stress. Furthermore, chronic stress exacerbated the damage of BBB integrity with the decreased expression of zonula occludens-1 (ZO-1), claudin-5 and occludin in brain vasculature, overactivated microglia and increased neuroinflammation in FruD mice. These results suggest that high fructose intake combined with chronic stress leads to cumulative negative effects that promote the development of depressive-like behaviors in mice. Of note, SCFAs could rescue hippocampal neurogenesis decline, improve BBB damage and suppress microglia activation and neuroinflammation, thereby ameliorate depressive-like behaviors of FruD mice exposed to chronic stress. These results could be used to develop dietary interventions to prevent depression.

Possibility of magnesium supplementation for supportive treatment in patients with COVID-19.

Magnesium as an enzymatic activator is essential for various physiological functions such as cell cycle, metabolic regulation, muscle contraction, and vasomotor tone. A growing body of evidence supports that magnesium supplementation (mainly magnesium sulfate and magnesium oxide) prevents or treats various types of disorders or diseases related to respiratory system, reproductive system, nervous system, digestive system, and cardiovascular system as well as kidney injury, diabetes and cancer. The ongoing pandemic coronavirus disease 19 (COVID-19) characterized by respiratory tract symptoms with different degrees of important organ and tissue damages has attracted global attention. Particularly, effective drugs are still lacking in the COVID-19 therapy. In this review, we find and summarize the effectiveness of magnesium supplementation on the disorders or diseases, and provide a reference to the possibility of magnesium supplementation for supportive treatment in patients with COVID-19.