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Down‐regulation of gephyrin and GABA A receptor subunits during epileptogenesis in the CA 1 region of hippocampus
Summary Purpose Epileptogenesis is the process by which a brain becomes hyperexcitable and capable of generating recurrent spontaneous seizures. In humans, it has been hypothesized that following a brain insult there are a number of molecular and cellular changes that underlie the development of spo...
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| Published in: | Epilepsia (Copenhagen) 2013-04, Vol.54 (4), p.616-624 |
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| Main Authors: | , , |
| Format: | Article |
| Language: | English |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
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Purpose
Epileptogenesis is the process by which a brain becomes hyperexcitable and capable of generating recurrent spontaneous seizures. In humans, it has been hypothesized that following a brain insult there are a number of molecular and cellular changes that underlie the development of spontaneous seizures. Studies in animal models have shown that an injured brain may develop epileptiform activity before appearance of epileptic seizures and that the pathophysiology accompanying spontaneous seizures is associated with a dysfunction of γ‐aminobutyric acid (
GABA
)ergic neurotransmission. Here, we analyzed the effects of status epilepticus on the expression of GABA
A
receptors (
GABA
A
Rs) and scaffolding proteins involved in the regulation of
GABA
A
R trafficking and anchoring.
Methods
Western blot analysis was used to determine the levels of proteins involved in
GABA
A
R
trafficking and anchoring in adult rats subjected to pilocarpine‐induced status epilepticus (
SE
) and controls. Cell surface biotinylation using a cell membrane–impermeable reagent was used to assay for changes in the expression of receptors at the plasma membrane. Finally, immunoprecipitation experiments were used to evaluate the composition of
GABA
A
Rs
. We examined for a correlation between total
GABA
A
R
subunit expression, plasma membrane expression, and receptor composition.
Key Findings
Analysis of tissue samples from the
CA
1 region of hippocampus show that
SE
promotes a loss of
GABA
A
R
subunits and of the scaffolding proteins associated with them. We also found a decrease in the levels of receptors located at the plasma membrane and alterations in
GABA
A
R
composition.
Significance
The changes in protein expression of
GABA
A
Rs
and scaffolding proteins detected in these studies provide a potential mechanism to explain the deficits in
GABA
ergic neurotransmission observed during the epileptogenic period. Our current observations represent an additional step toward the elucidation of the molecular mechanisms underlying
GABA
A
R
dysfunction during epileptogenesis. |
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| ISSN: | 0013-9580 1528-1167 |
| DOI: | 10.1111/epi.12063 |