Laboratory of Psychiatry and Experimental Alzheimer's Research, Department of Psychiatry and Psychotherapy, Innsbruck Medical University, Innsbruck, Austria.
Pharmacology. 2011;88(5-6):245-51. doi: 10.1159/000331861. Epub 2011 Oct 13.
A growing body of evidence indicates that hypoglycemia and acidosis may contribute to the development of Alzheimer's disease (AD). The cell death of basal forebrain cholinergic neurons constitutes a hallmark of AD and directly correlates with cognitive impairment. The aim of the present study was to investigate, in an organotypic rat brain slice model of the basal nucleus of Meynert, the effects of glucose deprivation on cholinergic neurons under normal and acidic conditions. Furthermore, we were interested to explore whether different saccharides (galactose, fructose, saccharose, lactose) can replace glucose under low pH conditions. Our data show a pH-dependent survival of cholinergic neurons at a high (37.1 mmol/l) glucose level, which was markedly decreased at a low (5.6 mmol/l) glucose level. Galactose (+31.5 mmol/l) significantly counteracted the loss of choline acetyltransferase-positive neurons in low-glucose-treated slices, while fructose, lactose and saccharose only partly protected cholinergic neurons. In conclusion, our results indicate that replacement of glucose with different saccharides, but most potently with galactose, protects cholinergic neurons against hypoglycemia at a low pH.
越来越多的证据表明，低血糖和酸中毒可能导致阿尔茨海默病（AD）的发生。基底前脑胆碱能神经元的细胞死亡是 AD 的一个标志，与认知障碍直接相关。本研究的目的是在 Meynert 基底核的器官型大鼠脑片模型中，研究在正常和酸性条件下葡萄糖剥夺对胆碱能神经元的影响。此外，我们还研究了在低 pH 条件下，不同的糖（半乳糖、果糖、蔗糖、乳糖）是否可以替代葡萄糖。我们的数据显示，在高（37.1mmol/l）葡萄糖水平下，胆碱能神经元的存活依赖于 pH，而在低（5.6mmol/l）葡萄糖水平下，其存活明显下降。半乳糖（+31.5mmol/l）显著抑制了低糖处理切片中胆碱乙酰转移酶阳性神经元的丢失，而果糖、乳糖和蔗糖仅部分保护了胆碱能神经元。总之，我们的结果表明，用不同的糖（最有效的是半乳糖）替代葡萄糖可以保护胆碱能神经元免受低血糖和低 pH 的影响。
