Neurotrophin and neuropeptide expression in mouse brain is regulated by knockout of the norepinephrine transporter
Neurotrophin and neuropeptide expression in mouse brain is regulated by knockout of the norepinephrine transporter
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DOI：
10.1007/s00702-008-0039-2
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发表时间：
2008-07-01
影响因子：
3.3
通讯作者：
Boenisch, H.
中科院分区：
文献类型：
--
作者：
Haenisch, B.;Gilsbach, R.;Boenisch, H.
神经营养因子[例如神经生长因子（NGF）、脑源性神经营养因子（BDNF）和神经营养因子 - 3（NT - 3）]以及神经肽如促肾上腺皮质激素释放因子（CRF）据报道有助于抗抑郁药（ADs）的作用。去甲肾上腺素转运体（NET）基因敲除（NETKO）小鼠代表一种慢性抗抑郁药治疗模型。在本研究中，我们分别通过实时定量聚合酶链反应（qPCR）和双位点酶联免疫吸附测定（ELISAs）检测了NET野生型（NETWT）和NETKO小鼠中NT - 3、NGF、BDNF和CRF在信使核糖核酸（mRNA）和蛋白质水平上的脑区特异性调节。在嗅球、脑干和全脑的mRNA水平以及嗅球的蛋白质水平检测到NETKO诱导的NT - 3变化，在嗅球、小脑和脑干的NGF mRNA和蛋白质水平以及海马体的CRF mRNA和蛋白质水平也检测到变化。相比之下，BDNF水平保持不变。我们的研究结果表明，NETKO小鼠是一种有用的模型，可用于检测可能参与抗抑郁药作用的下游靶点的基因调控。我们可以描绘出NT - 3、NGF和CRF在NET基因敲除后在不同脑区受到调控。
Neurotrophins [e.g. nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3)] and neuropeptides such as corticotropin-releasing factor (CRF) are reported to contribute to the action of antidepressants (ADs). Norepinephrine transporter (NET) knockout (NETKO) mice represent a model of chronic AD treatment. In the present study, we examined brain-region-specific regulations of NT-3, NGF, BDNF and CRF at the mRNA and protein level in NET wild-type (NETWT) and NETKO mice by means of quantitative real-time PCR (qPCR) and two-site enzyme-linked immunosorbent assays (ELISAs), respectively. NETKO-induced changes were detected for NT-3 in olfactory bulb, brainstem and whole brain at the mRNA and for olfactory bulb at the protein level, for NGF mRNA and protein in olfactory bulb, cerebellum and brainstem and for CRF mRNA and protein in the hippocampus. In contrast, BDNF levels remained unaltered. Our results suggest that NETKO mice represent a useful model to examine gene regulation of downstream targets potentially involved in the action of ADs. We could delineate NT-3, NGF and CRF as being regulated in distinct brain regions by KO of the NET.