Effects of desipramine treatment on stress-induced up-regulation of norepinephrine transporter expression in rat brains.
Effects of desipramine treatment on stress-induced up-regulation of norepinephrine transporter expression in rat brains.
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DOI：
10.1007/s00213-014-3674-3
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发表时间：
2015-01
影响因子：
3.4
通讯作者：
Zhu, Meng-Yang
中科院分区：
文献类型：
--
作者：
Fan, Yan;Chen, Ping;Li, Ying;Ordway, Gregory A.;Zhu, Meng-Yang
许多研究表明，在体外和应激未成熟的大鼠中，地塞帕明(DMI)下调去甲肾上腺素转运体(Net)的表达。关于应激动物体内网状结构的调控，人们知之甚少。本研究旨在探讨DMI对应激大鼠Net和蛋白激酶表达的影响。成年Fischer 344只大鼠接受4周的慢性社会挫败(CSD)。DMI(10 mg/kg，腹腔注射)与CSD同时给药或在CSD停止后1~2周给药。测量蔗糖消耗量、净表达和蛋白激酶。CSD显著增加蓝斑Net信使RNA(MRNA)和蛋白水平，以及海马区、额叶皮质和杏仁核Net蛋白水平。当DMI与CSD同时给药时，这些影响几乎被消除。CSD诱导的蓝斑、海马区和杏仁核Net表达上调在CSD停止后至少持续2周，这种作用在CSD停止后接受1或2周的DMI治疗后显著减弱。同时给予DMI和CSD并不显著干扰CSD诱导的这些脑区蛋白激酶A和C的蛋白水平的下降，但它确实逆转了CSD引起的大多数脑区磷酸化cAMP反应元件结合(PCREB)蛋白水平的下降。这些发现表明，DMI对应激大鼠和行为幼稚大鼠都有净调节作用，这可能与DMI诱导的pCREB变化有关。
Many studies demonstrate down-regulation of the norepinephrine transporter (NET) by desipramine (DMI) in vitro and in stress-naive rats. Little is known regarding regulation of the NET in stressed animals. The present study was designed to investigate effects of DMI on the expression of NET and protein kinases in the stress rat. Adult Fischer 344 rats were subjected to chronic social defeat (CSD) for 4 weeks. DMI (10 mg/kg, intraperitoneal (i.p.)) was administered concurrently with CSD or 1 or 2 weeks after cessation of CSD. Sucrose consumption, NET expression, and protein kinases were measured. CSD significantly increased messenger RNA (mRNA) and protein levels of NET in the locus coeruleus, as well as NET protein levels in the hippocampus, frontal cortex, and amygdala. These effects were nearly abolished when DMI was administered concurrently with CSD. CSD-induced up-regulation of NET expression in the locus coeruleus, hippocampus, and amygdala lasted at least 2 weeks after cessation of CSD, an effect that was significantly attenuated by 1 or 2 weeks of DMI treatment starting from cessation of the CSD. Concurrent administration of DMI with CSD did not markedly interfere with CSD-induced decreases in protein levels of protein kinases A and C in these brain regions, but it did reverse the CSD-induced reduction in phosphorylated cAMP response element-binding (pCREB) protein levels in most brain regions. These findings suggest that NET regulation by DMI occurs in both stressed and behaviorally naive rats, and DMI-induced changes in pCREB may be involved.
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影响因子：
2.9
作者：
BAUER, ME;TEJANIBUTT, SM
通讯作者：
TEJANIBUTT, SM
影响因子：
2.9
作者：
GUITART, X;KOGAN, JH;NESTLER, EJ
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NESTLER, EJ
影响因子：
7.3
作者：
IVERSEN, LL
通讯作者：
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7.6
作者：
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通讯作者：
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影响因子：
2.9
作者：
DHABHAR, FS;MCEWEN, BS;SPENCER, RL
通讯作者：
SPENCER, RL