Bassant M H, Poindessous-Jazat F, Schmidt B H
INSERM U 159, 2ter rue d'Alésia, 75014, Paris, France.
Eur J Pharmacol. 2000 Jan 10;387(2):151-62. doi: 10.1016/s0014-2999(99)00742-6.
To evaluate the influence of cholinergic projections from the basal forebrain on brain metabolism, we measured the cerebral metabolic rate of glucose (CMR(glu)) after unilateral lesioning of cholinergic basal forebrain neurons with the immunotoxin 192 IgG-saporin. CMR(glu) was determined in 24 cortical and 13 sub-cortical regions using the [14C]2-deoxy-D-glucose technique of Sokoloff. Average hemispheric CMR(glu) decreased by 7% (P<0.02) and 5% (P<0.05), 7 and 21 days after lesion, respectively. Regional effects were restricted to parietal and retrosplenial cortices, lateral habenula and the basal forebrain. We have previously shown that metrifonate increased CMR(glu) in intact rats. In lesioned rats, metrifonate (80 mg/kg, i. p.) was still active but the metabolic activation was reduced in terms of both the average hemispheric CMR(glu) and the number of regions significantly affected. Although it is reduced, the sustained effect of metrifonate in lesioned rats makes an argument for the use of this compound as treatment of cholinergic deficit in Alzheimer's disease.
为评估基底前脑胆碱能投射对脑代谢的影响，我们在用免疫毒素192 IgG-皂草素单侧损毁胆碱能基底前脑神经元后，测量了葡萄糖脑代谢率（CMR(glu)）。使用索科洛夫的[14C]2-脱氧-D-葡萄糖技术，在24个皮质区域和13个皮质下区域测定CMR(glu)。损毁后7天和21天，平均半球CMR(glu)分别下降了7%（P<0.02）和5%（P<0.05）。区域效应局限于顶叶和压后皮质、外侧缰核和基底前脑。我们之前已经表明，敌百虫可增加完整大鼠的CMR(glu)。在损毁大鼠中，敌百虫（80 mg/kg，腹腔注射）仍然有效，但就平均半球CMR(glu)和受显著影响的区域数量而言，代谢激活作用有所降低。尽管有所降低，但敌百虫在损毁大鼠中的持续作用为将该化合物用于治疗阿尔茨海默病的胆碱能缺陷提供了依据。
