
Synaptic Dysfunction in the Anterior Cingulate Cortex Underlies Pain‐Anxiety Comorbidity in a Mandibular Asymmetry Mouse Model
简介:
- 作者: Zhaoyichun Zhang, Yanran Zhang, Jialin Si, Honghui Mao, Feng He, Jin Ning, Guaiguai Ma, Xiaohua Chen, Haoxiang Xiao, Yuanyuan Zhu, Haifeng Zhang, Yifan Lu, Qian Liu, Meng Nian, Shiquan Sun, Shibin Yu, Shengxi Wu, Ze Fan, Zuolin Jin, Jing Huang
- 杂志: Advanced Science
- Doi: https://www.doi.org/10.1002/advs.202509509
- 出版日期: 2025/9/24
摘要
Structural craniofacial abnormalities, particularly mandibular asymmetry (MA), are increasingly recognized as key drivers of orofacial pain and emotional comorbidities, although the underlying neural mechanisms remain unclear. This study aims to develop a preclinical MA model to investigate the dynamic interplay between craniofacial structural defects and neurobehavioral dysfunction. Longitudinal behavioral phenotyping including von Frey filaments test as well as open field and elevated plus maze tests reveals progressive sensory hypersensitivity and anxiety-like behaviors, with computational ethology revealing subtle but consistent alterations in the naturalistic behaviors. Whole-brain activity mapping reveal hyperactivation in the anterior cingulate cortex (ACC), whereas multi-omics profiling reveal cell type-specific transcriptional changes and synaptic reorganization within this region. Functional investigation including sparse labeling, electrophysiology, western blotting, and chemogenetics demonstrate that the ACC modulation regulated both pain and anxiety. These findings establish a causal association between structural craniofacial defects and maladaptive neural circuit remodeling, with the ACC emerging as a critical therapeutic target. The study provides a comprehensive framework for understanding how anatomical abnormalities translate into persistent neurological dysfunction and offers new avenues for mechanistically informed intervention.
关于派真
作为一家专注于AAV 技术十余年,深耕基因治疗领域的CRO&CDMO,派真生物可提供从载体设计、构建到 AAV、慢病毒和 mRNA 服务的一站式解决方案。凭借深厚的技术实力、卓越的运营管理和高标准的服务交付,我们为全球客户提供一站式CMC解决方案,包括从早期概念验证、成药性评估到IIT、IND及BLA的各个阶段。
凭借我们独立知识产权的π-alphaTM 293 细胞AAV高产技术平台,我们能将AAV产量提高多至10倍,每批次产量可达1×10¹⁷vg,以满足多样化的商业化和临床项目需求。此外,我们定制化的mRNA和脂质纳米颗粒(LNP)产品及服务覆盖药物和疫苗开发的各个阶段,从研发到符合GMP的生产,提供端到端的一站式解决方案。
