2. Academic Validation
  3. Neuronal HIPK2-HDAC3 axis regulates mitochondrial fragmentation to participate in stroke injury and post-stroke anxiety like behavior

Neuronal HIPK2-HDAC3 axis regulates mitochondrial fragmentation to participate in stroke injury and post-stroke anxiety like behavior

  • Exp Neurol. 2024 Oct:380:114906. doi: 10.1016/j.expneurol.2024.114906.
Mengmeng Yang 1,  Hongrui Zhu 2,  Li Peng 3,  Tianyue Yin 3,  Shuaijie Sun 1,  Yuhao Du 3,  Jun Li 4,  Jinya Liu 4,  Sheng Wang 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology, First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China; Wannan Medical College, Wuhu 241002, China.
  • 2 Department of Anesthesiology, First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China. Electronic address: zhuhongrui@mail.ustc.edu.cn.
  • 3 Department of Anesthesiology, First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China; Core Facility Center, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Hefei, Anhui 230001, China.
  • 4 Department of Anesthesiology, First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.
  • 5 Department of Anesthesiology, First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China. Electronic address: iamsheng2020@ustc.edu.cn.
PMID: 39079624 DOI: 10.1016/j.expneurol.2024.114906
Abstract

Post-stroke anxiety (PSA) seriously affects the prognosis of patients, which is an urgent clinical problem to be addressed. However, the pathological mechanism of PSA is largely unclear. Here, we found that neuronal HIPK2 expression was upregulated in the ischemic lesion after stroke. The upregulation of HIPK2 promotes Drp1 oligomerization through the HDAC3-dependent pathway, leading to excessive mitochondrial damage. This subsequently triggers the release of cellular cytokines such as IL-18 from neurons under ischemic stress. Microglia are capable of responding to IL-18, which promotes their activation and enhances their phagocytosis, ultimately resulting in the loss of synapses and neurons, thereby exacerbating the pathological progression of PSA. HIPK2 knockdown or inhibition suppresses excessive pruning of neuronal synapses by activated microglia in the contralateral vCA1 region to compromise inactivated anxiolytic pBLA-vCA1Calb1+ circuit, relieving anxiety-like behavior after stroke. Furthermore, we discovered that early remimazolam administration can remodel HIPK2-HDAC3 axis, ameliorating the progression of PSA. In conclusion, our study revealed that the neuronal HIPK2-HDAC3 axis in the ischemic focus regulates mitochondrial fragmentation to balance inflammation stress reservoir to participate in anxiety susceptibility after stroke.

Keywords

HIPK2 mitochondrial dynamics; Neuroinflammation; Post-stroke anxiety.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-100464
    99.03%, HIPK2 抑制剂
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z