Jalonen T O, Charniga C J, Wielt D B
Division of Neurosurgery, Albany Medical College, NY 12208, USA.
Brain Res. 1997 Jan 23;746(1-2):85-97. doi: 10.1016/s0006-8993(96)01189-4.
Alzheimer's disease (AD) is a slowly progressing neurodegenerative disease characterized by the loss of neurons and formation of amyloid plaques, often surrounded by reactive astrocytes. Astrocytes are important regulators of the normal neuronal environment, and changed astrocyte function may lead to increased neuronal vulnerability. The slow onset of the disease with a gradual increase in the beta-amyloid peptide (beta-AP) concentrations may alter astrocyte function long before any visible symptoms of the disease are observed. We, therefore, studied in vitro the effects of small amounts of beta-AP(1-40) and -(25-35) on rat cortical astrocyte function observing changes in cell morphology, intracellular calcium levels (Cai), and ion channel activity. Incubation with 10 and 200 nM beta-APs caused increased process formation and hypertrophy. Stellation was also detected when astrocyte cultures were incubated with 1 microM AlCl3 alone, or together with beta-APs. Fura-2AM-loaded astrocytes were used to test whether the morphological changes were connected to changes in Cai levels. 1 microM beta-AP(1-40) induced transient Cai increase in approximately 17%, and beta-AP(25-35) in approximately 36% of astrocytes. In patch-clamp studies, increased K+ and Cl- channel activity was detected with 10-100 nM beta-AP(1-40). With large amounts (20 microM) of beta-AP(1-40), an additional giant channel activity emerged. These beta-AP-induced changes in astrocyte function may eventually be critical for the neuronal survival in Alzheimer's disease.
阿尔茨海默病（AD）是一种进展缓慢的神经退行性疾病，其特征为神经元丧失和淀粉样斑块形成，这些斑块常被反应性星形胶质细胞环绕。星形胶质细胞是正常神经元环境的重要调节者，星形胶质细胞功能改变可能导致神经元易损性增加。该疾病起病缓慢，β-淀粉样肽（β-AP）浓度逐渐升高，这可能在疾病出现任何明显症状之前很久就改变了星形胶质细胞的功能。因此，我们在体外研究了少量β-AP（1-40）和β-AP（25-35）对大鼠皮质星形胶质细胞功能的影响，观察细胞形态、细胞内钙水平（Cai）和离子通道活性的变化。用10 nM和200 nM的β-AP孵育导致突起形成增加和细胞肥大。当星形胶质细胞培养物单独用1 μM氯化铝或与β-AP一起孵育时，也检测到了星形化。用Fura-2AM负载的星形胶质细胞来测试形态变化是否与Cai水平的变化有关。1 μM的β-AP（1-40）在约17%的星形胶质细胞中诱导了短暂的Cai升高，β-AP（25-35）在约36%的星形胶质细胞中诱导了短暂的Cai升高。在膜片钳研究中，用10 - 100 nM的β-AP（1-40）检测到钾离子和氯离子通道活性增加。使用大量（20 μM）的β-AP（1-40）时，出现了额外的巨通道活性。这些β-AP诱导的星形胶质细胞功能变化最终可能对阿尔茨海默病中神经元的存活至关重要。
