Programmed and induced phenotype of the hippocampal granule cells
Programmed and induced phenotype of the hippocampal granule cells
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DOI：
10.1523/jneurosci.1674-05.2005
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发表时间：
2005-07-27
影响因子：
5.3
通讯作者：
Gutiérrez, R
中科院分区：
文献类型：
--
作者：
Gómez-Lira, G;Lamas, M;Gutiérrez, R
某些神经元以活动依赖的方式选择它们使用的神经递质，营养因子在发育过程中参与了这种表型分化。发育中的海马颗粒细胞（GCs）组成性地表达谷氨酸能和氨基丁酸能表型的标记物，但当发育完成时，氨基丁酸能表型关闭。通过电生理、单细胞反转录- PCR和免疫组织学技术，我们在这里发现，表达谷氨酸、VGlut- 1（泡状谷氨酸转运蛋白）mRNA、calbindin和dynorphin mRNA的完全分化成年谷氨酸能GCs的短期（24小时）培养可以诱导其重新表达GABA能标记物GABA、GAD（谷氨酸脱羧酶67 kDa亚型）和VGAT（泡状谷氨酸转运蛋白）mRNA。用脑源性神经营养因子（BDNF）持续突触或直接激活谷氨酸受体和激活TrkB（酪氨酸受体激酶B）受体（30分钟）。gaba能标记物的表达可通过阻断谷氨酸受体和钠钙通道、抑制蛋白激酶和蛋白合成来阻止。在癫痫大鼠的海马切片和BDNF处理的幼稚大鼠的切片中，我们证实了在谷氨酸受体阻滞剂存在的情况下，单突触GABA(A)受体介导的对GC刺激的反应。因此，从这些切片制备的GC培养物显示谷氨酸能和gaba能标记物的共表达。我们的研究结果表明，就其在整个生命中持续的出生和死亡而言，GCs的神经递质选择是独一无二的，它取决于程序和环境因素，这一过程既不受关键发育时期的限制，也不受其在自然网络中的插入的限制。
Certain neurons choose the neurotransmitter they use in an activity- dependent manner, and trophic factors are involved in this phenotypic differentiation during development. Developing hippocampal granule cells ( GCs) constitutively express the markers of the glutamatergic and GABAergic phenotypes, but when development is completed, the GABAergic phenotype shuts off. With electrophysiological, single- cell reverse transcription- PCR and immunohistological techniques, we show here that short- term ( 24 h) cultures of fully differentiated adult glutamatergic GCs, which express glutamate, VGlut- 1 ( vesicular glutamate transporter) mRNA, calbindin, and dynorphin mRNA, can be induced to reexpress the GABAergic markers GABA, GAD(67) ( glutamate decarboxylase 67 kDa isoform), and VGAT ( vesicular GABA transporter) mRNA, by sustained synaptic or direct activation of glutamate receptors and by activation of TrkB ( tyrosine receptor kinase B) receptors, with brain- derived neurotrophic factor ( BDNF) ( 30 min). The expression of the GABAergic markers was prevented by the blockade of glutamate receptors and sodium or calcium channels, and by inhibitors of protein kinases and protein synthesis. In hippocampal slices of epileptic rats and in BDNF- treated slices from naive rats, we confirmed the appearance of monosynaptic GABA(A) receptor- mediated responses to GC stimulation, in the presence of glutamate receptors blockers. Accordingly, GC cultures prepared from these slices showed the coexpression of the glutamatergic and GABAergic markers. Our results demonstrate that the neurotransmitter choice of the GCs, which are unique in terms of their continuing birth and death throughout life, depends on programmed and environmental factors, and this process is neither limited by a critical developmental period nor restricted by their insertion in their natural network.