Scholarlink

<p>Dietary advanced glycation end products (AGEs) and chronic stress might be involved in psychiatric disorders. It remains unclear whether dietary AGEs and chronic stress work together to trigger anxiety and depression. Firstly, mice were subjected to dietary AGEs (12 weeks) combined with chronic restraint stress (weeks 9–12, with daily restraint in a 50-mL cylindrical plastic tube for 3–4 h), defined as CRA group. Combined exposure aggravated anxiety-like and depression-like behaviors, disrupted gut microbiota homeostasis, induced inflammation, shifted tryptophan (TRP) metabolism towards kynurenine (KYN) pathway, mainly characterized by elevated KYN and 3-hydroxykynurenine (3-HK), and induced ferroptosis in the hippocampus. Secondly, IDO1 inhibitor, 1-methyltryptophan (1-MT), restored the TRP-KYN pathway disturbance post CRA, and inhibited neuronal ferroptosis post CRA. Thirdly, the ferroptosis inhibitor ferrostatin-1 restored CRA-induced neuronal ferroptosis, but had no effect on the TRP-KYN pathway. KYN and 3-HK induced ferroptosis in the mouse hippocampal neuron cell line (HT22), consistent with in vivo experimental results. In conclusion, combined exposure may first disturb gut microbiota homeostasis, followed by intestinal inflammatory responses, subsequently triggering tryptophan towards kynurenine metabolism via the gut-brain axis. These pathological processes led to the abnormal accumulation of neurotoxic metabolites, i.e., KYN and 3-HK, within neurons, which then induced neuronal ferroptosis.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Dietary advanced glycation products combined with chronic restraint stress induced anxiety-like and depression-like behaviors in male mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月8日

查看全文
  • Yebing Zhang,
  • Kuiying Gu,
  • Lili Xin,
  • Yu Xia,
  • Guoqi Yang,
  • Jiejiao Cai,
  • Zhilong He,
  • Li-Qiang Qin,
  • Zhongxiao Wan

摘要

Dietary advanced glycation end products (AGEs) and chronic stress might be involved in psychiatric disorders. It remains unclear whether dietary AGEs and chronic stress work together to trigger anxiety and depression. Firstly, mice were subjected to dietary AGEs (12 weeks) combined with chronic restraint stress (weeks 9–12, with daily restraint in a 50-mL cylindrical plastic tube for 3–4 h), defined as CRA group. Combined exposure aggravated anxiety-like and depression-like behaviors, disrupted gut microbiota homeostasis, induced inflammation, shifted tryptophan (TRP) metabolism towards kynurenine (KYN) pathway, mainly characterized by elevated KYN and 3-hydroxykynurenine (3-HK), and induced ferroptosis in the hippocampus. Secondly, IDO1 inhibitor, 1-methyltryptophan (1-MT), restored the TRP-KYN pathway disturbance post CRA, and inhibited neuronal ferroptosis post CRA. Thirdly, the ferroptosis inhibitor ferrostatin-1 restored CRA-induced neuronal ferroptosis, but had no effect on the TRP-KYN pathway. KYN and 3-HK induced ferroptosis in the mouse hippocampal neuron cell line (HT22), consistent with in vivo experimental results. In conclusion, combined exposure may first disturb gut microbiota homeostasis, followed by intestinal inflammatory responses, subsequently triggering tryptophan towards kynurenine metabolism via the gut-brain axis. These pathological processes led to the abnormal accumulation of neurotoxic metabolites, i.e., KYN and 3-HK, within neurons, which then induced neuronal ferroptosis.