浙江大学王福俤团队取得一项新突破。他们提出了铁可塑性通过海马腹侧铁-α-突触核蛋白轴驱动社会隔离引起的焦虑。2026年1月27日出版的《细胞—代谢》发表了这项成果。

该研究组在这里报道，社会隔离通过糖皮质激素启动的铁-α-突触核蛋白（α-Syn）轴在腹侧海马（vHip）锥体神经元中触发“铁可塑性”——一种新型的经验依赖性突触重构形式。社会心理压力特别影响这一途径。从机制上讲，分离诱导的糖皮质激素受体激活上调转铁蛋白受体1 (TfR1)，导致神经元铁积累，从而通过翻译抑制促进α-Syn表达。α-Syn随后增强谷氨酸释放和脊柱密度，导致髋关节过度兴奋和焦虑。针对任何节点的TfR1-铁α-Syn轴的干预可以预防或逆转焦虑样行为，建立必要性和因果性。通过鼻内给药铁螯合剂或靶向α- synn的反义寡核苷酸（ASO）可使vHip神经活动正常化并缓解焦虑，这为临床翻译提供了一条直接可行的途径。他们的发现将铁塑性定义为社会压力病理学的核心机制，将脑铁代谢与情感障碍联系起来。

据悉，社会孤立是焦虑症的主要环境驱动因素，但其神经生物学基础仍然是未知的。

附：英文原文

Title: Ferroplasticity drives social isolation-induced anxiety via a ventral hippocampal iron-α-synuclein axis

Author: Zhuo Wang, Sifan Yang, Tianrong Huang, Jinhui Zhao, Shuangyi Tan, Yuhan Zhang, Tianming Lü, Pingming Qiu, Junxia Min, Fudi Wang

Issue&Volume: 2026-01-27

Abstract: Social isolation is a major environmental driver of anxiety disorders, yet its neurobiological underpinnings remain elusive. We report here that social isolation triggers “ferroplasticity”—a novel form of experience-dependent synaptic remodeling—in ventral hippocampus (vHip) pyramidal neurons via a glucocorticoid-initiated iron-α-synuclein (α-Syn) axis. Psychosocial stress specifically engages this pathway. Mechanistically, isolation-induced glucocorticoid receptor activation upregulates transferrin receptor 1 (TfR1), leading to neuronal iron accumulation, which boosts α-Syn expression via translational derepression. α-Syn then enhances glutamate release and spine density, driving vHip hyperexcitability and anxiety. Interventions targeting the TfR1-iron-α-Syn axis at any node prevent or reverse anxiety-like behaviors, establishing necessity and causality. Translationally, intranasal delivery of an iron chelator or α-Syn-targeting antisense oligonucleotide (ASO) normalizes vHip neural activity and alleviates anxiety, highlighting a direct and viable path to clinical translation. Our findings define ferroplasticity as a core mechanism in social stress pathology, bridging brain iron metabolism with affective disorders.

DOI: 10.1016/j.cmet.2025.12.022

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00586-8