Related Experiment Video

Updated: Jun 24, 2025

Caspase-3 Activity in the Rat Amygdala Measured by Spectrofluorometry After Myocardial Infarction
08:41

Caspase-3 Activity in the Rat Amygdala Measured by Spectrofluorometry After Myocardial Infarction

Published on: January 12, 2016

11.8K

Pharmacological inhibition of cGAS ameliorates postoperative cognitive dysfunction by suppressing

Xueshan Bu1, Ping Gong2, Lei Zhang1

  • 1Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.

Neurochemistry International
|June 6, 2024
PubMed

Insights

Inhibiting the cGAS-STING pathway reduces neuroinflammation and cognitive decline after surgery. This approach dampens pyroptosis, offering a potential treatment for postoperative cognitive dysfunction (POCD).

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Neuroinflammation significantly contributes to postoperative cognitive dysfunction (POCD).
  • The cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) pathway is implicated in neuroinflammation but its role in POCD is unclear.

Purpose of the Study:

  • To investigate the role of the cGAS-STING pathway in POCD pathogenesis.
  • To evaluate the therapeutic potential of cGAS inhibition in a mouse model of POCD.

Main Methods:

  • A POCD mouse model was induced using isoflurane anesthesia and laparotomy.
  • Mice and BV2 cells were treated with a cGAS inhibitor (RU.521) or a caspase-3 agonist (Raptinal).
  • Cognitive function, neuroinflammation markers, and pyroptosis indicators were assessed using behavioral tests, Western blot, ELISA, and TUNEL staining.

Main Results:

  • Isoflurane/laparotomy increased cGAS levels and cytoplasmic dsDNA accumulation.
  • RU.521 treatment improved cognitive function, reduced inflammatory cytokines (TNFα, IL-6), and inhibited pyroptosis markers (cleaved caspase-3, N-GSDME, IL-1β, IL-18).
  • The protective effects of RU.521 were reversed by Raptinal.

Conclusions:

  • The cGAS-STING pathway plays a critical role in POCD development.
  • Pharmacological inhibition of cGAS mitigates neuroinflammation and cognitive impairment in POCD by suppressing caspase-3/GSDME-dependent pyroptosis.
  • Targeting the cGAS pathway presents a promising therapeutic strategy for POCD.
Keywords:
Caspase-3GSDMEPostoperative cognitive dysfunctionPyroptosisSTINGcGAS

More Related Videos

Chemogenetic Regulation in Reprogrammed Stem Cell-derived Precursor Cells in Treating Neurodegenerative Diseases09:44

Chemogenetic Regulation in Reprogrammed Stem Cell-derived Precursor Cells in Treating Neurodegenerative Diseases

Published on: May 2, 2025

139
Colon Ascendens Stent Peritonitis CASP - a Standardized Model for Polymicrobial Abdominal Sepsis06:45

Colon Ascendens Stent Peritonitis CASP - a Standardized Model for Polymicrobial Abdominal Sepsis

Published on: December 18, 2010

19.5K

Related Concept Videos

GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.5K
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
6.0K
Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists01:30

Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists

Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function.
120
General Anesthesia: Overview01:24

General Anesthesia: Overview

Anesthesia is a medical procedure that uses drugs for CNS suppression to enable painless surgeries and procedures. The selection of anesthetics is influenced by their pharmacokinetic properties, side effects, and patient characteristics. Various types of anesthesia include general, local, regional, spinal, and inhalational.
General anesthesia induces unconsciousness in the whole body, while the others target specific areas or sensations. It is administered to minimize adverse effects, maintain...
212
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.2K