C8-ceramide modulates microglia BDNF expression to alleviate postoperative cognition dysfunction via PKCδ/NF-κB

Guangqian Li1, Yuhao Wang2,3, Lei Qian1

  • 1Department of Anesthesiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, #32 West Second Section, First-Ring Road, Chengdu, 610072, People's Republic of China.

PubMed

Insights

C8-ceramide enhances brain-derived neurotrophic factor (BDNF) expression in microglia, offering a potential treatment for postoperative cognitive dysfunction (POCD). This drug improved cognitive function in mice by targeting the PKCδ/NF-κB pathway.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Postoperative cognitive dysfunction (POCD) is a significant complication following general anesthesia, impacting patient recovery.
  • Activated microglia and their inflammatory cytokine secretions play a key role in POCD pathogenesis.
  • Brain-derived neurotrophic factor (BDNF) exhibits anti-inflammatory and neuroprotective properties, making it a target for POCD treatment.

Purpose of the Study:

  • To investigate the regulatory effect of C8-ceramide on BDNF expression in microglia.
  • To assess the therapeutic potential of C8-ceramide in a mouse model of POCD.
  • To elucidate the molecular mechanism underlying C8-ceramide's effects on POCD.

Main Methods:

  • Primary microglia were treated with lipopolysaccharide (LPS) and C8-ceramide in vitro.
  • A mouse model of POCD was established using carotid artery exposure.
  • Cognitive function and the PKCδ/NF-κB signaling pathway were analyzed in treated mice.

Main Results:

  • C8-ceramide upregulated BDNF mRNA expression in LPS-stimulated primary microglia.
  • C8-ceramide treatment significantly improved cognitive deficits in mice with POCD.
  • The drug enhanced cognitive function through the PKCδ/NF-κB signaling pathway.

Conclusions:

  • C8-ceramide stimulates microglia to increase BDNF expression, counteracting POCD.
  • This study identifies a novel molecular mechanism involving PKCδ/NF-κB signaling in C8-ceramide's therapeutic effects.
  • C8-ceramide presents a promising new clinical strategy for treating postoperative cognitive dysfunction.

Related Concept Videos

Long-term Depression01:05

Long-term Depression

Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Long-term Depression01:03

Long-term Depression

Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
Calcium Ion Concentration Mechanism
If over time, all...
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...
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. They...
Gut-Brain Axis01:22

Gut-Brain Axis

The gut–brain axis is a bidirectional communication system that connects the gastrointestinal tract and the brain. This interaction is mediated through multiple pathways, including the vagus nerve, hormonal signals, immune responses, and chemical messengers produced by gut microbes.Microbial Contributions to Brain FunctionGut microbiota contributes significantly to brain function by producing neuroactive compounds. These include neuroactive compounds that influence neurotransmitters such as...