Bourdiol F, Fage D, Serrano A, Carter C, Benavides J, Scatton B
Synthélabo Recherche, LERS, Department of Biology, Bagneux, France.
Brain Res. 1992 Nov 20;596(1-2):183-8. doi: 10.1016/0006-8993(92)91546-q.
The injection into the rat striatum of the polyamines spermine and spermidine (30-300 nmol) produced, 1 week after injection, a dose related loss of the neuronal markers glutamate decarboxylase and choline acetyltransferase and a decrease in the density of N-methyl-D-aspartate (NMDA) receptors (as labelled with [3H]TCP). In parallel, an increase in peripheral type benzodiazepine (p) binding site density (a marker of the associated glial reaction and macrophage invasion) was observed. Intrastriatal injection of putrescine (300 nmol) did not significantly alter any of these markers. The effect of spermine on these neuronal and glial markers was maximal 3 days after injection, and tended towards control levels at 16 days post injection. The neurotoxic effects of spermine were confirmed by histological analysis demonstrating a massive neuronal loss around the injection site and an accumulation of astrocytes and phagocytes. The neurotoxic effects of spermine (250 nmol) were not antagonised by the previous administration of the NMDA receptor antagonist MK-801 (10 mg/kg, i.p.). Thus polyamine neurotoxicity in vivo does not seem to involve NMDA receptor activation, although it may possibly be related to the multiple effects of these compounds on diverse calcium channels and processes regulating calcium homoeostasis.
向大鼠纹状体注射多胺精胺和亚精胺（30 - 300纳摩尔），在注射1周后，导致神经元标志物谷氨酸脱羧酶和胆碱乙酰转移酶呈剂量依赖性丧失，以及N - 甲基 - D - 天冬氨酸（NMDA）受体密度降低（用[³H]TCP标记）。同时，观察到外周型苯二氮䓬（p）结合位点密度增加（这是相关胶质反应和巨噬细胞浸润的标志物）。纹状体内注射腐胺（300纳摩尔）并未显著改变这些标志物中的任何一项。精胺对这些神经元和胶质标志物的影响在注射后3天达到最大，在注射后16天趋于对照水平。组织学分析证实了精胺的神经毒性作用，显示注射部位周围大量神经元丧失以及星形胶质细胞和吞噬细胞积聚。精胺（250纳摩尔）的神经毒性作用未被预先给予的NMDA受体拮抗剂MK - 801（10毫克/千克，腹腔注射）拮抗。因此，体内多胺神经毒性似乎不涉及NMDA受体激活，尽管它可能与这些化合物对多种钙通道和调节钙稳态过程的多种作用有关。
