焦虑症发病机制复杂，现有药物尚不能满足临床需要。因此，发掘新的治疗策略成为临床迫切需求。颗粒蛋白前体（Progranulin，PGRN）是一种多功能的分泌性生长因子，广泛表达于中枢，参与中枢炎症调节。PGRN 作为肿瘤坏死因子受体（TNFR）的一种新配体而备受关注。我们前期研究发现，与焦虑相关的杏仁核区域高表达PGRN；杏仁核局部给予PGRN可显著抑制外周炎症引起的小鼠焦虑样行为；形态学研究发现PGRN可显著增强杏仁核神经棘突的发育，成熟型棘突显著增加，并增强皮层-杏仁核通路突触可塑性；提示PGRN在焦虑治疗中的潜在价值。本项目首次提出PGRN能够快速调节杏仁核兴奋性/抑制性突触传递平衡，通过TNFR干扰中枢炎症反应，可望成为抗焦虑药物作用的新靶点。本研究拟采用基因干涉、电生理和行为学等方法，探讨PGRN对杏仁核神经环路的调节，为阐明焦虑症发病机制及发掘药物新靶点提供理论依据。

Anxiety is one of the most common psychiatric disorders. Because of its complex pathogenesis, the existing anxiolytic drugs cannot meet the clinical requirements. Therefore, it is urgent to explore new therapeutic strategies for clinical treatment. Progranulin (PGRN) is a multifunctional secreted growth factor, which is widely expressed in the central nervous system. PGRN as a new ligand of tumor necrosis factor receptor (TNFR) has attracted much attention. Our previous study found that PGRN highly expressed in the anxiety-related amygdala region. Amygdala local infusion of PGRN could significantly inhibit the peripheral inflammation induced anxiety like behavior. Morphological studies found that PGRN significantly enhanced the development of neural spines, increased the percentage of mature spines process significantly, and enhanced cortex-amygdala synaptic plasticity. These results prompt the potential value of PGRN in the treatment of anxiety. It is the first time to propose that PGRN regulates the inhibitory and excitatory synaptic transmission in the amygdala, which may be a new target of anxiolytic drugs through binding TNFR. Multiple methods such as genetic modulation, molecular biology, electrophysiology, and behavioral test will be used to explore the role of PGRN in amygdala neural circuits. This project will be helpful to elucidate the mechanisms underlying the pathogenesis of anxiety disorders and to provide a theoretical basis for target of novel anxiolytics.