Differential effects of neonatal norepinephrine lesions on immediate early gene expression in developing and adult rat brain.
Differential effects of neonatal norepinephrine lesions on immediate early gene expression in developing and adult rat brain.
复制标题
DOI：
10.1016/j.neuroscience.2008.09.036
复制
发表时间：
2008-12-10
期刊：
影响因子：
3.3
通讯作者：
Murrin LC
中科院分区：
文献类型：
--
作者：
Sanders JD;Happe HK;Bylund DB;Murrin LC
Arc、c-fos和zif 268是对成人脑可塑性非常重要的即刻早期基因。目前的研究探讨了这些IEG的发育表达和新生儿去甲肾上腺素能损伤对其表达的影响，在发育和成熟的大脑。在出生后第3天（PND 3）给予特异性去甲肾上腺素能神经毒素N-（2-氯乙基）-N-乙基-2-溴苄胺盐酸盐（DSP-4），在PND 13、25和60采用原位杂交技术检测Arc、c-fos和zif 268 mRNA的表达。与成熟脑去甲肾上腺素能病变引起的Arc、c-fos和zif 268表达的降低相反，PND 3的病变产生了显著不同的效果。新生儿病变在PND 13时产生特定额叶皮质层中c-fos和zif 268表达的增加，而Arc显示无变化。这些病变导致PND 25时额叶皮质层中zif 268表达增加，而c-fos或Arc表达无变化，并且在PND 60时，它们导致海马中c-fos表达显著增加，而Arc或zif 268表达无显著变化。RX 821002是一种A2 AR拮抗剂，给予对照PND 60动物，产生Arc、zif 268和c-fos mRNA的升高。在PND 3用DSP-4损伤的动物中消除了该反应。这些数据表明，IEG表达的去甲肾上腺素调节在发育和成熟的大脑中是不同的，并且发育去甲肾上腺素的丧失导致出生后IEG表达异常高。一些研究已经表明去甲肾上腺素在脑发育中的重要作用，包括突触密度和神经元形态的调节。我们的数据支持的想法，去甲肾上腺素在中枢神经系统的发展过程中发挥重要作用，在发展过程中去甲肾上腺素能信号的变化可能会有长期持久的影响，可能对学习和记忆。
Arc, c-fos and zif268 are immediate early genes (IEGs) important for adult brain plasticity. The current study examines developmental expression of these IEGs and the effect of neonatal noradrenergic lesion on their expression in developing and mature brain. N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), a specific noradrenergic neurotoxin, was administered to rats on postnatal day (PND) 3 and in situ hybridization was used to assay Arc, c-fos and zif268 mRNA on PND 13, 25 and 60. In contrast to decreases in Arc, c-fos and zif268 expression produced by noradrenergic lesions of mature brain, lesions on PND3 yield a strikingly different effect. Neonatal lesions produce increases in c-fos and zif268 expression in specific frontal cortical layers on PND13, while Arc shows no change. These lesions lead to increases in zif268 expression in frontal cortical layers on PND 25, with no changes in c-fos or Arc expression, and on PND60 they produce a significant increase in c-fos expression in hippocampus with no significant changes in Arc or zif268 expression. RX821002, an A2AR antagonist, administered to control PND 60 animals produces elevations of Arc, zif268 and c-fos mRNAs. This response was eliminated in animals lesioned with DSP-4 on PND 3. These data indicate that norepinephrine regulation of IEG expression differs in developing and mature brain and that the loss of developmental norepinephrine leads to abnormally high postnatal IEG expression. Several studies have shown an important role for norepinephrine in brain development, including the regulation of synaptic densities and neuronal morphology. Our data support the idea that norepinephrine plays an important role during CNS development and that changes in noradrenergic signaling during development may have long lasting effects, potentially on learning and memory.
登录
查看更多内容
DOI：
10.1073/pnas.95.5.2313
发表时间：
1998-03-03
影响因子：
11.1
作者：
Crino, P;Khodakhah, K;Eberwine, J
通讯作者：
Eberwine, J
影响因子：
3.2
作者：
GRZANNA, R;BERGER, U;GEFFARD, M
通讯作者：
GEFFARD, M
影响因子：
3.3
作者：
JONSSON, G;HALLMAN, H;SUNDSTROM, E
通讯作者：
SUNDSTROM, E
影响因子：
56.9
作者：
Frankland, PW;Bontempi, B;Silva, AJ
通讯作者：
Silva, AJ
影响因子：
3.4
作者：
Herry, C;Mons, N
通讯作者：
Mons, N