食生活の多様性とうつ病および自殺の有病率との関連 ―26年間の国際比較研究―

Purpose: This study aimed to determine the associations of dietary diversity with depression and suicide rates by an ecological analysis using 26-years worldwide statistics.Methods: Average food supply and energy supply by country, excluding loss between production and household, were obtained from the Food and Agriculture Organization of the United Nations Statistics Division database (FAOSTAT). Dietary diversity scores were calculated from food group classifications. Age-standardized depression prevalence and suicide rates per 100,000 people by country were obtained from the Global Burden of Disease (GBD) 2017 database. The association between food diversity scores and depression prevalence and suicide rates was analyzed by a mixed effects model controlling for covariates in 137 countries with populations of 1 million or greater.Results: A significant negative association was found in the analysis of the relationship between dietary diversity and the prevalence of major depression in the model controlled for all covariates [β (se) = –225.6 (61.9), p < 0.001]. In addition, a significant negative association between dietary diversity and the suicide rate was also found in the model controlled for all covariates [β (se) = –3.08 (1.50), p < 0.05].Conclusion: Dietary diversity was significantly negatively associated with the rates of major depression and suicide. Diets rich in foods may reduce the prevalence of depression and suicide rate.【目的】本研究は、26年間の世界的な統計を用いた生態学的分析により、食生活の多様性とうつ病や自殺率との関連を明らかにすることを目的とした。【方法】生産と家庭間の喪失を除く国別平均食料供給量とエネルギー供給量を国連食糧農業機関統計局データベース（FAOSTAT）から入手した。食物群分類から食事多様性スコアを算出した。年齢標準化された国別の人口10万人当たりのうつ病有病率と自殺率は、Global Burden of Disease（GBD）2017データベースから取得した。人口100万人以上の137カ国を対象に、食品多様性スコアとうつ病有病率および自殺率との関連を、共変量を制御した混合効果モデルで解析した。【結果】食生活の多様性とうつ病の有病率との関係を分析したところ、すべての共変量を調整したモデルにおいて、有意な負の関連が認められた［β（se）＝－225.6（61.9）、p < 0.001］。さらに、食生活の多様性と自殺率との間の有意な負の関連も、すべての共変量を調整したモデルで認められた［β（se）= －3.08（1.50）、p < 0.05］。【結論】食生活の多様性は、うつ病および自殺の発生率と有意に負の関連があった。食物を豊富に含む食事は、うつ病や自殺を減少させる可能性がある

The neuroprotective effects of FG-4592, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, against oxidative stress induced by alpha-synuclein in N2a cells

Abstract Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. The pathological hallmark of PD is the appearance of intraneuronal cytoplasmic α-synuclein (α-Syn) aggregation, called Lewy bodies. α-Syn aggregation is deeply involved in the pathogenesis of PD. Oxidative stress is also associated with the progression of PD. In the present study, to investigate whether a hypoxia-inducible factor (HIF)-prolyl hydroxylase (PH) inhibitor, FG-4592 (also called roxadustat), has neuroprotective effects against α-Syn-induced neurotoxicity, we employed a novel α-Syn stably expressing cell line (named α-Syn-N2a cells) utilizing a piggyBac transposon system. In α-Syn-N2a cells, oxidative stress and cell death were induced by α-Syn, and FG-4592 showed significant protection against this neurotoxicity. However, FG-4592 did not affect α-Syn protein levels. FG-4592 triggered heme oxygenase-1 (HO-1) expression downstream of HIF-1α in a concentration-dependent manner. In addition, FG-4592 decreased the production of reactive oxygen species possibly via the activation of HO-1 and subsequently suppressed α-Syn-induced neurotoxicity. Moreover, FG-4592 regulated mitochondrial biogenesis and respiration via the induction of the peroxisome proliferator-activated receptor-γ coactivator-1α. As FG-4592 has various neuroprotective effects against α-Syn and is involved in drug repositioning, it may have novel therapeutic potential for PD

Kaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro

Aggregation of α-synuclein (α-Syn) is implicated in the pathogenesis of Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Therefore, the removal of α-Syn aggregation could lead to the development of many new therapeutic agents for neurodegenerative diseases. In the present study, we succeeded in generating a new α-Syn stably expressing cell line using a piggyBac transposon system to investigate the neuroprotective effect of the flavonoid kaempferol on α-Syn toxicity. We found that kaempferol provided significant protection against α-Syn-related neurotoxicity. Furthermore, kaempferol induced autophagy through an increase in the biogenesis of lysosomes by inducing the expression of transcription factor EB and reducing the accumulation of α-Syn; thus, kaempferol prevented neuronal cell death. Moreover, kaempferol directly blocked the amyloid fibril formation of α-Syn. These results support the therapeutic potential of kaempferol in diseases such as synucleinopathies that are characterized by α-Syn aggregates