Related Experiment Video

Updated: Aug 2, 2026

Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders
07:43

Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders

Published on: May 12, 2015

NMDA receptor/L-VGCC-dependent expression and AMPA/KA receptor-dependent activation of c-Jun induced by cerebral

Quan-Guang Zhang1, Yong-Ling Xu, Hong-Chun Li

  • 1Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu 221002, PR China.

Neuroscience Letters
|February 2, 2006
PubMed

Insights

Excitotoxicity from glutamate receptor over-activation damages neurons. This study shows N-methyl-D-aspartate (NMDA) receptors and L-type voltage-gated calcium channels (L-VGCC) control c-Jun expression, while AMPA/KA receptors control its activation during ischemic brain damage.

Area of Science:

  • Neuroscience
  • Cellular Biology
  • Biochemistry

Background:

  • Excitotoxicity, caused by over-activated ionotropic glutamate receptors, leads to excessive calcium influx and neuronal death.
  • The JNK-c-Jun signaling pathway plays a critical role in ischemic brain injury.
  • Understanding the specific roles of different glutamate receptors and calcium channels in this pathway is crucial for developing neuroprotective strategies.

Purpose of the Study:

  • To investigate the effects of modulating ionotropic glutamate receptors and L-type voltage-gated calcium channels (L-VGCC) on c-Jun expression and activation in the hippocampus following transient global ischemia in Sprague-Dawley rats.
  • To differentiate the roles of N-methyl-D-aspartate (NMDA) receptors and AMPA/kainate (AMPA/KA) receptors in regulating the JNK-c-Jun pathway during ischemic insult.

Main Methods:

  • Transient global ischemia was induced in Sprague-Dawley rats.
  • Western blotting was used to assess total c-Jun protein levels and phosphorylation.
  • Electrophoretic mobility shift assay (EMSA) was employed to evaluate AP-1 binding activity.
  • Pharmacological agents including ketamine (NMDA receptor antagonist), nifedipine (L-VGCC blocker), and DNQX (AMPA/KA receptor antagonist) were used for pretreatment.

Main Results:

  • Ischemia-reperfusion significantly increased total c-Jun protein levels, peaking at 3-6 hours of reperfusion.
  • Ketamine and nifedipine pretreatment prevented the increase in total c-Jun expression, indicating NMDA receptor and L-VGCC dependence.
  • DNQX pretreatment inhibited c-Jun phosphorylation, which was significantly increased at 3 hours of reperfusion, suggesting AMPA/KA receptor involvement in c-Jun activation.
  • EMSA results corroborated Western blotting findings regarding AP-1 binding activity.

Conclusions:

  • c-Jun protein expression following ischemic brain injury is dependent on NMDA receptor and L-VGCC activity.
  • c-Jun activation, specifically phosphorylation, is regulated by AMPA/KA receptor signaling.
  • These findings elucidate the distinct roles of different glutamate receptor subtypes and calcium channels in the JNK-c-Jun pathway, contributing to a better understanding of ischemic brain damage mechanisms.

More Related Videos

Slice Patch Clamp Technique for Analyzing Learning-Induced Plasticity11:56

Slice Patch Clamp Technique for Analyzing Learning-Induced Plasticity

Published on: November 11, 2017

Horizontal Hippocampal Slices of the Mouse Brain08:59

Horizontal Hippocampal Slices of the Mouse Brain

Published on: September 22, 2020

Related Concept Videos

Long-term Potentiation01:35

Long-term Potentiation

Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre- and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
Long-term Potentiation01:25

Long-term Potentiation

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