Developmental DSP4 effects on cortical Arc expression.
Developmental DSP4 effects on cortical Arc expression.
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DSP4 发育对皮质 Arc 表达的影响。
DOI：
10.1016/j.neulet.2016.02.063
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发表时间：
2016
影响因子：
2.5
通讯作者：
Sanders,Jeff
中科院分区：
文献类型：
--
作者：
Sanders,Jeff
活性调节细胞骨架相关蛋白（Activity Regulated Cytoskeleton Associated Protein，Arc）是一种对脑可塑性起关键作用的即刻早期基因。在这项研究中，去甲肾上腺素的调节ARC表达在出生后的不同阶段进行了检查。在大鼠青春期前（PND 0或13）、青春期（PND 23或48）和成年期（PND 60）注射选择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）。在每次DSP 4处理后，在发育后期收获脑，并在原位杂交中分析ArcmRNA水平。与生理盐水处理的对照组相比，青春期前用DSP 4损伤的大鼠在ARC水平上没有差异。相反，青春期是一个改变ArcmRNA响应DSP 4的时间。在青春期早期损伤的大鼠显示ARC表达增加，而在青春期晚期损伤的大鼠显示ARC表达显著减少。青少年后期DSP 4引起的ARC水平下降与在受损成人中发现的相似。这些研究结果突出了一个质的不同的调节去甲肾上腺素的ARC表达根据发展阶段，并表明，成熟的调节是不完整的，直到青春期后期。这些数据表明去甲肾上腺素对大脑可塑性的调节存在重要的发育差异。这些差异可能是儿童和青少年与成人相比精神反应差异的基础。
Activity Regulated Cytoskeleton Associated Protein (Arc) is an immediate early gene that is critical to brain plasticity. In this study, norepinephrine’s regulation ofArcexpression was examined during different stages of postnatal development. Rats were injected withN-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), a selective noradrenergic neurotoxin, during preadolescence (PND 0 or 13), adolescence (PND 23 or 48) or adulthood (PND 60). After each DSP4 treatment, brains were harvested later in development andArcmRNA levels analyzed within situhybridization. Rats lesioned with DSP4 during preadolescence showed no differences inArclevel compared to saline treated controls. In contrast, adolescence was a time of changingArcmRNA response to DSP4. Rats lesioned during early adolescence showedArcexpression increases, while rats lesioned during late adolescence showed dramaticArcexpression decreases. Decreases inArclevel caused by late adolescent DSP4 were similar to those found in lesioned adults. These findings highlight a qualitatively different regulation ofArcexpression by norepinephrine according to developmental stage, and indicate that mature regulation is not intact until late adolescence. These data point to important developmental differences in norepinephrine’s regulation of brain plasticity. These differences may underlie contrasting psychotropic responses in children and adolescents compared to adults.