2. Academic Validation
  3. AMPA receptor potentiation alleviates NLRP3 knockout-induced fear generalization in mice

AMPA receptor potentiation alleviates NLRP3 knockout-induced fear generalization in mice

  • Biochem Biophys Res Commun. 2024 May 23:722:150074. doi: 10.1016/j.bbrc.2024.150074.
Weifen Li 1,  Qichao Gong 2,  Wenhui Zhu 3,  Tahir Ali 4,  Zhi-Jian Yu 5,  Shupeng Li 6,  Xiaoming Yu 7
Affiliations

Affiliations

  • 1 Department of Infectious Diseases and Shenzhen key laboratory for endogenous infections, the 6th Affiliated Hospital of Shenzhen University Health Science Center, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China; State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China. Electronic address: 2206395065@pku.edu.cn.
  • 2 State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China. Electronic address: gongqch@stu.pku.edu.cn.
  • 3 Southern Medical University, Nanfang Hospital, Department of Laboratory Medicine, Guangzhou, 510515, Guangdong, China. Electronic address: 792029310@qq.com.
  • 4 State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China. Electronic address: tali@bs.qau.edu.pk.
  • 5 Department of Infectious Diseases and Shenzhen key laboratory for endogenous infections, the 6th Affiliated Hospital of Shenzhen University Health Science Center, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China. Electronic address: yuzhijiansmu@163.com.
  • 6 State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China. Electronic address: lisp@pku.edu.cn.
  • 7 Cancer Center, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, China. Electronic address: yuxiaoming1927@email.sdu.edu.cn.
PMID: 38805785 DOI: 10.1016/j.bbrc.2024.150074
Abstract

Genetic knockout and pharmaceutical inhibition of the NLRP3 inflammasome enhances the extinction of contextual fear memory, which is attributed to its role in neuronal and synaptic dysregulation, concurrent with neurotransmitter function disturbances. This study aimed to determine whether NLRP3 plays a role in generalizing fear via the inflammatory axis. We established the NLRP3 KO mice model, followed by behavioral and biochemical analyses. The NLRP3 KO mice displayed impaired fear generalization, lower neuroinflammation levels, and dysregulated neurotransmitter function. Additionally, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, but not the inhibition of NMDA or 5-HT2C receptors, resulted in fear generalization in NLRP3 KO mice because TAT-GluA2 3Y, but not SB242084 and D-cycloserine, treated blocked NLRP3 deprivation effects on fear generalization. Thus, global knockout of NLRP3 is associated with aberrant fear generalization, possibly through AMPA Receptor signaling.

Keywords

AMPA receptor; Fear generalization; Hippocampus; NLRP3; Neuroinflammation; Neurotransmitter.

Figures
Products
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