Jhamandas Jack H, Harris Kim H, MacTavish David, Jassar Balvinder S
Division of Neurology, Department of Medicine, University of Alberta, 530 Heritage Medical Research Centre, Edmonton, Alberta T6G 2S2, Canada.
J Neurophysiol. 2002 Feb;87(2):696-704. doi: 10.1152/jn.00416.2001.
Galanin, a 29-amino-acid neuropeptide, is generally viewed as an inhibitory neuromodulator in a variety of central systems. Galanin expression is upregulated in the cholinergic basal forebrain nuclei in Alzheimer's disease (AD) and is postulated to play an important role in memory and cognitive function. In this study, application of galanin to acutely dissociated rat neurons from the basal forebrain nucleus diagonal band of Broca (DBB), caused a decrease in whole cell voltage-activated currents in a majority of cells. Galanin reduces a suite of potassium currents, including calcium-activated potassium (I(C)), the delayed rectifier (I(K)), and transient outward potassium (I(A)) conductances, but not calcium or sodium currents. Under current-clamp conditions, application of galanin evoked an increase in excitability and a loss of accommodation in cholinergic DBB neurons. Using single-cell RT-PCR technique, we determined that galanin actions were specific to cholinergic, but not GABAergic DBB neurons The notion that galanin plays a deleterious role in AD is based, in part, on galanin hyperinnervation of cholinergic cells in the basal forebrain of AD patients, its ability to depress acetylcholine release and its inhibitory actions at other CNS sites. However, our results suggest that by virtue of its excitatory actions on cholinergic neurons, galanin may in fact play a compensatory role by augmenting the release of acetylcholine from remaining cholinergic basal forebrain neurons. This action might serve to delay the progression of AD pathology linked to a reduction in central cholinergic tone.
甘丙肽是一种由29个氨基酸组成的神经肽，在各种中枢系统中通常被视为一种抑制性神经调质。在阿尔茨海默病（AD）中，胆碱能基底前脑核中的甘丙肽表达上调，并被认为在记忆和认知功能中起重要作用。在本研究中，将甘丙肽应用于从布罗卡斜角带基底前脑核急性分离的大鼠神经元，导致大多数细胞的全细胞电压激活电流降低。甘丙肽减少了一系列钾电流，包括钙激活钾电流（I(C)）、延迟整流钾电流（I(K)）和瞬时外向钾电流（I(A)），但不影响钙电流或钠电流。在电流钳制条件下，应用甘丙肽可引起胆碱能斜角带基底前脑神经元的兴奋性增加和适应性丧失。使用单细胞逆转录聚合酶链反应技术，我们确定甘丙肽的作用对胆碱能斜角带基底前脑神经元具有特异性，而对γ-氨基丁酸能神经元无特异性。甘丙肽在AD中起有害作用这一观点部分基于AD患者基底前脑胆碱能细胞的甘丙肽过度支配、其抑制乙酰胆碱释放的能力以及在其他中枢神经系统部位的抑制作用。然而，我们的结果表明，由于甘丙肽对胆碱能神经元的兴奋作用，它实际上可能通过增加剩余胆碱能基底前脑神经元的乙酰胆碱释放而发挥代偿作用。这一作用可能有助于延缓与中枢胆碱能张力降低相关的AD病理进展。
