GluR-B Protein Is Upregulated in CA1 Injured Neurons Following Status Epilepticus in Prebubescent Rats.
Abstract number :
A.01
Submission category :
Year :
2001
Submission ID :
948
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
L.K. Friedman, PhD, Neuroscience, NJ Neuroscience Institute, So Orange, NJ; H. Liu, MD/PhD, Neuroscience, NJ Neuroscience Institute, So Orange, NJ; B. Magrys, BS, Neuroscience, NJ Neuroscience Institute, So Orange, NJ; J. Kaur, PhD, Neurosience, NJ Neuros
RATIONALE: AMPA receptors lacking the edited form of the GluR-B subunit have been implicated in delayed cell death after recurrent seizures or global ischemia. However, decreases, increases or sustained levels of the GluR-B subunit occur within sclerotic regions. Following ischemia tolerance, GluR-B expression is increased in CA1 neurons. Moreover, the temporal relationship between AMPA receptor subunit composition and excitotoxicity is incompatible with the long biological half-life of the GluR-B subunit in CA1 neurons.
METHODS: The present study examined the effects of single or multiple seizures, induced by kainate (KA), on GluR-A, GluR-B, NR1 and NR2A/B hippocampal levels in prepubescent rats that exhibit preferential CA1 seizure-induced damage. To examine seizure-induced tolerance, status epilepticus was induced once or three times on postnatal ages (P6, P9, P20, or P30).
RESULTS: Three days after one episode of status epilepticus induced on P20, immunohistochemical analysis showed that GluR-A and GluR-B proteins were simultaneously downregulated in CA1 neurons. At P30, GluR-A immunolabeling was depleted in CA1 and only the morphologically healthy cells were labeled. In contrast, the GluR-B subunit was highly upregulated but marked only the injured CA1 neurons. In CA3/hilus, the GluR-A subunit was sustained or increased in scattered pyramidals or interneurons. GluR-B expression was preferentially decreased in CA3, which resembled the adult pattern. NR1 and NR2A/B proteins were sustained in both regions at both ages. Decreases for all proteins examined were associated with cell loss. Previous exposure to two neonatal seizures (at P6 and P9) raised the seizure threshold and reduced the extent of neuronal damage and changes in GluR-A and GluR-B expression patterns, particularly in the P20 age group.
CONCLUSIONS: The observations presented do not support the original assumption that formation of Ca[2+] permeable AMPA receptors induces neuronal cell death. An opposite interpretation is proposed such that both GluR-A and GluR-B subunits play important roles in acquisition of seizure/hypoxia-induced tolerance rather than delayed neurodegeneration. Since the overall pattern of neuronal injury was not influenced by a history of neonatal seizures the intensity of activity and maturation of excitatory anatomy and function are responsible for the damage.