Differential gene expression of neonatal and adult DRG neurons correlates with the differential sensitization of TRPV1 responses to nerve growth factor.

Differential gene expression of neonatal and adult DRG neurons correlates with the differential sensitization of TRPV1 responses to nerve growth factor.
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DOI:
10.1016/j.neulet.2011.06.034
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发表时间:
2011-08-18
影响因子:
2.5
通讯作者:
Oxford GS
Oxford GS
中科院分区:
医学4区
文献类型:
--
作者:
Zhu W;Oxford GS

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新生儿和成人背根神经节(DRG)神经元的培养物通常用于体外模型,以研究各种条件下与外周感觉相关的离子通道和信号事件。新生儿和成人DRG神经元对生理或病理刺激的差异反应表明其基因表达谱存在潜在差异。我们对培养的成年和新生大鼠DRG神经元进行了微阵列分析,揭示了不同的基因表达谱,特别是在基因组水平上的离子通道和信号分子。例如,Ca 2+刺激的腺苷酸环化酶(AC)亚型AC 3和AC 8,PKCδ和CaMK II α,电压门控钠通道β1和β4,以及钾通道Kv1.1,Kv3.2,Kv4.1,Kv9.1,Kv9.3,Kir3.4,Kir7.1,K2P1.1/TWIK-1在成年大鼠DRG神经元中具有显著较高的mRNA表达,而Ca 2+抑制AC 5和AC 6,钠通道Nav1.3 α亚基、钾通道Kir6.1 K2P10.1/TREK-2、钙通道Cav2.2 α1亚基及其辅助亚基β1和β3在成年神经元中表达下调。重要的是,发现并通过PCR和western blot证实了ERK 1/2、PI 3 K/P110α的较高表达,而不是TRPV 1和TrkA。后者的这些发现与ERK和PI 3 K信号传导在NGF致敏TRPV 1中的关键作用一致,并且可以解释我们先前发表的观察结果,即成年大鼠DRG神经元而不是新生大鼠DRG神经元被NGF致敏。
Cultures of neonatal and adult dorsal root ganglion (DRG) neurons are commonly used in in vitro models to study the ion channels and signaling events associated with peripheral sensation under various conditions. Differential responsiveness between neonatal and adult DRG neurons to physiological or pathological stimuli suggests potential differences in their gene expression profiles. We performed a microarray analysis of cultured adult and neonatal rat DRG neurons which revealed distinct gene expression profiles especially of ion channels and signaling molecules at the genomic level. For example, Ca2+-stimulated adenylyl cyclase (AC) isoforms AC3 and AC8, PKCδ and CaMKIIα, the voltage-gated sodium channel β1 and β4, and potassium channels Kv1.1, Kv3.2, Kv4.1, Kv9.1, Kv9.3, Kir3.4, Kir7.1, K2P1.1/TWIK-1 had significantly higher mRNA expression in adult rat DRG neurons, while Ca2+-inhibited AC5 and AC6, sodium channel Nav1.3 α subunit, potassium channels Kir6.1 K2P10.1/TREK-2, calcium channel Cav2.2 α1 subunit, and its auxiliary subunits β1 and β3 were conversely down regulated in adult neurons. Importantly, higher adult neuron expression of ERK1/2, PI3K/P110α, but not of TRPV1 and TrkA, was found and confirmed by PCR and western blot. These latter findings are consistent with the key role of ERK and PI3K signaling in sensitization of TRPV1 by NGF and may explain our previously published observation that adult, but not neonatal, rat DRG neurons are sensitized by NGF.
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