Avallone Jennifer, Gashi Eleonora, Magrys Bonaventure, Friedman Linda K
New York College of Osteopathic Medicine of New York Institute of Technology, Old Westbury, NY 11568, USA.
Exp Neurol. 2006 Nov;202(1):100-11. doi: 10.1016/j.expneurol.2006.05.033. Epub 2006 Jul 25.
The effects of repeated neonatal seizures on metabotropic glutamate receptors (mGluRs) during critical periods of brain development are unknown. Therefore, we characterized the expression of Group I (mGluR1 and mGluR5) and Group II (mGluR2/3) metabotropic glutamate receptor proteins in the developing limbic system in response to a varied neonatal seizure history. Status epilepticus was induced with kainic acid (KA) either once (1x KA) on postnatal (P) day (P13), twice (2x KA) on P6 and P9 or P13, or three times (3x KA) on P6, P9, and P13. In control hippocampus, mGluR1alpha protein expression differed at all stages of development examined, whereas mGluR2/3 and mGluR5 protein expression patterns were mature by P15. After KA-induced status epilepticus, there was a significant elevation in mGluR1alpha protein expression within a select group of inhibitory interneurons of the CA1 stratum oriens-alveus that was enhanced with increasing number of neonatal seizures. mGluR2/3 and mGluR5 subtypes were unchanged. Increases were also observed within neurons of the amygdala and piriform cortex. Selective increases of mGluR1alpha subtypes within limbic structures may contribute to the resistance and tolerance of the immature hippocampus from damage. This may occur by excessive stimulation of excitatory synapses to collectively enhance the inhibitory drive of the immature brain by increasing GABA release. Data suggest that the mGluR1alpha subtype plays an important role in regulating hippocampal network activity after early-life seizures.
在大脑发育的关键时期，反复发生的新生儿癫痫发作对代谢型谷氨酸受体（mGluRs）的影响尚不清楚。因此，我们研究了在不同的新生儿癫痫发作史的情况下，发育中的边缘系统中I组（mGluR1和mGluR5）和II组（mGluR2/3）代谢型谷氨酸受体蛋白的表达情况。在出生后（P）第13天用一次海藻酸（KA）诱导癫痫持续状态（1x KA），在P6和P9或P13用两次（2x KA），或在P6、P9和P13用三次（3x KA）。在对照海马体中，mGluR1α蛋白表达在所有检测的发育阶段均有差异，而mGluR2/3和mGluR5蛋白表达模式在P15时成熟。KA诱导癫痫持续状态后，在CA1原层-肺泡层的一组选择性抑制性中间神经元中，mGluR1α蛋白表达显著升高，且随着新生儿癫痫发作次数的增加而增强。mGluR2/3和mGluR5亚型未发生变化。在杏仁核和梨状皮质的神经元中也观察到了增加。边缘结构中mGluR1α亚型的选择性增加可能有助于未成熟海马体抵抗和耐受损伤。这可能是通过过度刺激兴奋性突触，通过增加GABA释放来共同增强未成熟大脑的抑制驱动。数据表明，mGluR1α亚型在调节早期癫痫发作后的海马网络活动中起重要作用。
