- 作者: Cynthia J Gibson; Rebecca C Meyer; Robert J Hamm
- 作者服務機構: Department of Psychology, Washington College, Chestertown, MD, USA
- 中文摘要: --
- 英文摘要:
Background: Excitatory amino acid release and subsequent biochemical cascades following
traumatic brain injury (TBI) have been well documented, especially glutamate-related
excitotoxicity. The effects of TBI on the essential functions of inhibitory GABA-A receptors,
however, are poorly understood.
Methods: We used Western blot procedures to test whether in vivo TBI in rat altered the protein
expression of hippocampal GABA-A receptor subunits α1, α2, α3, α5, β3, and γ2 at 3h, 6h, 24h,
and 7 days post-injuy. We then used pre-injury injections of MK-801 to block calcium influx
through the NMDA receptor, diltiazem to block L-type voltage-gated calcium influx, or
diazepam to enhance chloride conductance, and re-examined the protein expressions of α1, α2,
α3, and γ2, all of which were altered by TBI in the first study and all of which are important
constituents in benzodiazepine-sensitive GABA-A receptors.
Results: Western blot analysis revealed no injury-induced alterations in protein expression for
GABA-A receptor α2 or α5 subunits at any time point post-injury. Significant time-dependent
changes in α1, α3, β3, and γ2 protein expression. The pattern of alterations to GABA-A subunits
was nearly identical after diltiazem and diazepam treatment, and MK-801 normalized expression
of all subunits 24 hours post-TBI.
Conclusions: These studies are the first to demonstrate that GABA-A receptor subunit
expression is altered by TBI in vivo, and these alterations may be driven by calcium-mediated
cascades in hippocampal neurons. Changes in GABA-A receptors in the hippocampus after TBI
may have far-reaching consequences considering their essential importance in maintaining
inhibitory balance and their extensive impact on neuronal function. - 中文關鍵字: --
- 英文關鍵字: --