Hervás-Aguilar A, Puebla-Jiménez L, Burgos-Ramos E, Aguado-Llera D, Arilla-Ferreiro E
Grupo de Neurobioquímica, Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Ctra. Madrid-Barcelona km 33,6, Universidad de Alcalá, E-28871, Alcalá de Henares, Madrid, Spain.
Neuroscience. 2005;135(1):181-90. doi: 10.1016/j.neuroscience.2005.02.017.
It is unknown whether the amyloid beta-peptide (Abeta), a principal component found in extracellular neuritic plaques in the brain of patients with Alzheimer's disease (AD), is capable of altering adenylyl cyclase (AC) activity and the somatostatin (SRIF) receptor-effector system in the cerebral cortex of the patients. Therefore, the objective of this study was to investigate the effect of the beta fragment, beta (25-35), on AC activity and the somatostatinergic system in the rat frontoparietal cortex. A single dose of beta (25-35) (10microg) injected intracerebroventricularly significantly decreased the density of SRIF receptors (27.4%) and increased their affinity (32.2%) in the frontoparietal cortex. The inhibitory effect of SRIF on basal and forskolin (FK)-stimulated AC activity was significantly lower in the beta (25-35)-treated rats when compared with controls. beta (25-35) did not modify Gialpha1, Gialpha2 nor Gialpha3 levels in membranes from the frontoparietal cortex. Continuous infusion of the peptide induced a decrease in the SRIF receptor density in this brain area to a similar extent as that observed 14 days after the single administration of the peptide. Likewise, this treatment decreased the SRIF receptor density in the frontal cortex (15.3%) and parietal cortex (27.2%). This effect was accompanied by a decrease in the SRIF-mediated inhibition of FK-stimulated AC activity (from 41.6% to 25.6%) in the frontal cortex as well by a decrease in basal AC activity (from 36.9% to 31.6%) and FK-stimulated AC activity (from 35.6% to 27.1%) in the parietal cortex. Continuous infusion of Abeta (25-35) had no effect on Gialpha1, Gialpha2 or Gialpha3 levels in membranes from frontal and parietal cortex. However, this treatment caused a decrease in SRIF-like immunoreactivity content in the parietal (38.9%) and frontal (20.4%) cortex. These results suggest that Abeta might be involved in the alterations of somatostatinergic system reported in AD.
尚不清楚β淀粉样肽（Aβ），即阿尔茨海默病（AD）患者大脑细胞外神经炎性斑块中的主要成分，是否能够改变患者大脑皮层中的腺苷酸环化酶（AC）活性和生长抑素（SRIF）受体效应系统。因此，本研究的目的是探究β片段β（25 - 35）对大鼠额顶叶皮层中AC活性和生长抑素能系统的影响。脑室内注射单剂量的β（25 - 35）（10微克）可显著降低额顶叶皮层中SRIF受体的密度（27.4%）并增加其亲和力（32.2%）。与对照组相比，在经β（25 - 35）处理的大鼠中，SRIF对基础和福斯高林（FK）刺激的AC活性的抑制作用显著降低。β（25 - 35）并未改变额顶叶皮层膜中Gialpha1、Gialpha2和Gialpha3的水平。持续输注该肽可使该脑区的SRIF受体密度降低，其程度与单次给药14天后观察到的相似。同样，这种处理降低了额叶皮层（15.3%）和顶叶皮层（27.2%）中的SRIF受体密度。这种效应伴随着额叶皮层中SRIF介导的对FK刺激的AC活性的抑制作用降低（从41.6%降至25.6%），以及顶叶皮层中基础AC活性降低（从36.9%降至31.6%）和FK刺激的AC活性降低（从35.6%降至27.1%）。持续输注Aβ（25 - 35）对额叶和顶叶皮层膜中Gialpha1、Gialpha2或Gialpha3的水平没有影响。然而，这种处理导致顶叶（38.9%）和额叶（20.4%）皮层中SRIF样免疫反应性含量降低。这些结果表明，Aβ可能参与了AD中报道的生长抑素能系统的改变。
