Department of Experimental and Applied Pharmacology, University of Pavia, Pavia, Italy.
J Alzheimers Dis. 2010;19(3):1041-53. doi: 10.3233/JAD-2010-1299.
We previously demonstrated that amyloid-beta (Abeta) has a neuromodulatory action in the nucleus accumbens (NAc). In this area of the brain, the peptide disrupts the cholinergic control of dopamine (DA) release both in vivo and in vitro. The aim of the present work was to extend the research on the neuromodulatory effect of Abeta (1-40) on DA transmission to different release stimuli and to another dopaminergic brain area, the caudate putamen (CPu), in order to clarify whether the effect of the peptide is stimulus- or brain area-selective. We performed both in vivo (microdialysis associated to HPLC) and in vitro studies (synaptosomes in superfusion). Both in NAc and in CPu and both in vivo and in vitro, Abeta did not affect either basal or potassium-stimulated DA release. In CPu, the Abeta ability to impair the DA release evoked by the cholinergic agonist carbachol, observed in NAc, was confirmed only in vitro. Moreover, in vitro Abeta affected a specific component of the DA overflow evoked by the non-selective metabotropic glutamate receptors agonist t-ACPD. Altogether, these results show that Abeta may have different neuromodulatory actions depending upon the secretory stimulus and, in vivo, the brain area investigated.
我们之前已经证明了淀粉样蛋白-β（Abeta）在伏隔核（NAc）中具有神经调节作用。在大脑的这个区域，该肽在体内和体外都破坏了多巴胺（DA）释放的胆碱能控制。本研究的目的是将 Abeta（1-40）对 DA 传递的神经调节作用的研究扩展到不同的释放刺激和另一个多巴胺能脑区尾壳核（CPu），以澄清该肽的作用是刺激还是脑区选择性的。我们进行了体内（与 HPLC 相关的微透析）和体外研究（共培养的突触体）。无论是在 NAc 还是 CPu 中，无论是在体内还是在体外，Abeta 都不会影响基础或钾刺激的 DA 释放。在 CPu 中，Abeta 损害 NAc 中观察到的由胆碱能激动剂卡巴胆碱引起的 DA 释放的能力仅在体外得到证实。此外，体外 Abeta 影响了由非选择性代谢型谷氨酸受体激动剂 t-ACPD 引起的 DA 溢出的特定成分。总之，这些结果表明，Abeta 可能具有不同的神经调节作用，这取决于分泌刺激，以及体内研究的脑区。
