Shen P J, Gundlach A L
The University of Melbourne, Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg, Victoria, 3084, Australia.
Exp Neurol. 1998 Dec;154(2):612-27. doi: 10.1006/exnr.1998.6915.
Noradrenaline, an important transmitter in the CNS, is involved in cerebral plasticity and functional recovery after injury. Experimental brain injury, including KCl application onto the brain surface, induces a slow-moving cortical depolarization/depression wave called cortical spreading depression (CSD). Interestingly, CSD does not produce neuronal damage but can protect cortical neurons against subsequent neurotoxic insults, although the mechanisms involved are unknown. This study examined the status of alpha- and beta-adrenoceptors (ARs) in cerebral cortex following CSD. Anesthetized rats had unilateral CSD induced by a 10-min topical application of KCl to the frontoparietal cortex and were killed at various times thereafter. Levels of alpha1-, alpha2-, beta1-, and beta2-AR mRNA and binding were examined using in situ hybridization histochemistry and radioligand autoradiography. Levels of alpha1b-AR mRNA in the affected neocortex were significantly increased by 20-40% at 1, 2, and 7 days (P </= 0.01) compared with contralateral levels, but were not significantly above control values at 2 and 4 weeks after CSD induction. Cortical alpha1B-AR binding sites were also increased by 45-65% 1 and 2 weeks (P </= 0.01) after CSD in a similar, but delayed, profile to alpha1b-AR mRNA. CSD rapidly increased beta1-AR mRNA by 45% at 1 h (P </= 0.01) and produced a delayed decrease of 25% in alpha2a-AR mRNA at 2 days and 1 week (P </= 0.05), but had no effect on corresponding levels of binding sites. In contrast, CSD had no effect on the remaining AR-subtype mRNAs or binding levels in neocortex under identical conditions. These results reveal a long-term up-regulation of alpha1B-ARs induced by an acute cortical stimulation/depression. Subtype-selective responses of ARs to CSD reflect an important differential regulation of expression of each receptor in vivo and suggest that alpha1B-ARs are particularly likely to be involved in cortical adaptive responses to physical injury at both local and distant locations.
去甲肾上腺素是中枢神经系统中的一种重要神经递质，参与脑损伤后的脑可塑性和功能恢复。实验性脑损伤，包括在脑表面应用氯化钾，会诱发一种缓慢移动的皮质去极化/抑制波，称为皮质扩散性抑制（CSD）。有趣的是，CSD不会造成神经元损伤，反而能保护皮质神经元免受随后的神经毒性损伤，尽管其中涉及的机制尚不清楚。本研究检测了CSD后大脑皮质中α和β肾上腺素能受体（ARs）的状态。将麻醉的大鼠单侧额叶顶叶皮质局部应用氯化钾10分钟诱导CSD，然后在不同时间点处死。使用原位杂交组织化学和放射性配体放射自显影技术检测α1、α2、β1和β2-AR mRNA水平及结合情况。与对侧水平相比，在受影响的新皮质中，α1b-AR mRNA水平在1天、2天和7天时显著升高20%-40%（P≤0.01），但在CSD诱导后2周和4周时并未显著高于对照值。皮质α1B-AR结合位点在CSD后1周和2周也增加了45%-65%（P≤0.01），其变化趋势与α1b-AR mRNA相似，但有延迟。CSD在1小时时使β1-AR mRNA迅速增加45%（P≤0.01），并在2天和1周时使α2a-AR mRNA延迟下降25%（P≤0.05），但对相应的结合位点水平没有影响。相比之下，在相同条件下，CSD对新皮质中其余AR亚型的mRNA或结合水平没有影响。这些结果揭示了急性皮质刺激/抑制诱导的α1B-ARs长期上调。ARs对CSD的亚型选择性反应反映了体内每种受体表达的重要差异调节，并表明α1B-ARs特别可能参与局部和远处对物理损伤的皮质适应性反应。
