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GluR2(B) knockdown accelerates CA3 injury after kainate seizures
Linda K Friedman1, Jana Velísková, Jaspreet Kaur
1Department of Neuroscience, Seton Hall University, South Orange, New Jersey 07079, USA. friedmli@shu.edu
Journal of Neuropathology and Experimental Neurology
|August 7, 2003
Summary
Reduced GluR2(B) expression accelerates kainate-induced seizures and CA3 neuron injury, suggesting apoptosis in CA3 neurons. Other factors may explain CA1 and DG neuron survival.
Area of Science:
- Neuroscience
- Cell Biology
- Neuropharmacology
Background:
- Calcium (Ca2+) influx through AMPA receptors is implicated in glutamate excitotoxicity.
- The GluR2(B) subunit of AMPA receptors limits Ca2+ permeability.
Purpose of the Study:
- To investigate if reduced GluR2(B) subunit expression enhances seizure-induced vulnerability in CA1 and CA3 neurons.
- To determine the role of GluR2(B) subunit in kainate-induced excitotoxicity.
Main Methods:
- Oligodeoxynucleotides (AS-ODNs) were used to reduce GluR2(B) expression in the dorsal hippocampus of adult rats.
- Kainate (KA) was administered to induce seizures (status epilepticus).
- Histological, electrographic, and behavioral analyses were performed, including TUNEL and immunohistochemistry.
Main Results:
- GluR2(B) knockdown accelerated kainate-induced histological injury, particularly in CA3a-b and hilar subregions.
- Apoptosis and necrosis were observed in CA3 neurons, with preferential injury to CA3a.
- While CA3 neurons showed accelerated injury, CA1 and DG neurons survived despite GluR2(B) loss, suggesting alternative survival mechanisms.
Conclusions:
- Hippocampal GluR2(B) subunit deprivation alone does not cause cell death but accelerates kainate-induced CA3/hilar lesions, potentially via apoptosis.
- CA1 and DG neuron survival suggests other intrinsic properties, not solely AMPA receptor Ca2+ permeability, contribute to augmented cell death.
- Altered AMPA receptor subunit expression and interactions with other receptor classes may play a role in seizure-induced neurotoxicity and tolerance.