Silva Virgília S, Cordeiro J Miguel, Matos Manuel J, Oliveira Catarina R, Gonçalves Paula P
Centro de Estudos do Ambiente e Mar, Departamento de Biologia, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
Neurosci Res. 2002 Oct;44(2):181-93. doi: 10.1016/s0168-0102(02)00128-1.
In the present work, we studied the effect of cholesterol/phospholipid (CH/PL) molar ratio on aluminum accumulation and aluminum-induced alteration of membrane fluidity in rat brain cortex synaptosomes. We observed that sub-acute (daily supply of 1.00 g of AlCl(3) during 10 days) and chronic (daily supply of 0.03 g of AlCl(3) during 4 months) exposure to dietary aluminum leads to a synaptosomal aluminum enrichment of 45 and 59%, respectively. During chronic exposure to AlCl(3), the enhancement of aluminum content was prevented by administration of colestipol (0.31 g/day), which decreased the synaptosomal membrane CH/PL molar ratio (nmol/nmol) from 1.2 to 0.4. Fluorescence anisotropy analysis, using 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene (TMA-DPH), showed that after treatment with colestipol a decrease in membrane order occurs at the level of hydrophilic lipid-water surface and deeper hydrophobic region of the synaptosomal membrane. When the rats were exposed to aluminum, it was observed a significant enhancement of membrane fluidity, which was more pronounced at the level of the membrane hydrophilic regions. Meanwhile, when chronic exposure to dietary AlCl(3) was accompanied by treatment with colestipol, the aluminum-induced decrease in membrane order was negligible when compared to TMA-DPH and DPH anisotropy values measured upon colestipol treatment. In contrast, in vitro incubation of synaptosomes (isolated from control rats) with AlCl(3) induced a concentration-dependent rigidification of this more hydrophilic membrane region. The opposite action of aluminum on synaptosomal membrane fluidity, during in vivo and in vitro experiments, appears to be explained by alteration of synaptosomal CH/PL molar ratio, since a significant reduction (approximately 80%) of this parameter occurs during in vivo exposure to aluminum. In conclusion, during in vivo exposure to aluminum, fluidification of hydrophilic regions and reduction of CH/PL molar ratio of presynaptic membranes accompany the accumulation of this cation, which appear to restrict aluminum retention in brain cortex nerve terminals.
在本研究中，我们研究了胆固醇/磷脂（CH/PL）摩尔比对大鼠脑皮质突触体中铝积累以及铝诱导的膜流动性改变的影响。我们观察到，亚急性（10天内每日供应1.00 g AlCl₃）和慢性（4个月内每日供应0.03 g AlCl₃）饮食铝暴露分别导致突触体铝富集45%和59%。在慢性暴露于AlCl₃期间，考来烯胺（0.31 g/天）的给药可防止铝含量的增加，考来烯胺使突触体膜CH/PL摩尔比（nmol/nmol）从1.2降至0.4。使用1,6 - 二苯基 - 1,3,5 - 己三烯（DPH）和1 - （4 - （三甲氨基）苯基） - 6 - 苯基己 - 1,3,5 - 三烯（TMA - DPH）的荧光各向异性分析表明，考来烯胺处理后，突触体膜亲水脂质 - 水表面和更深的疏水区域的膜有序性降低。当大鼠暴露于铝时，观察到膜流动性显著增强，这在膜亲水区域更为明显。同时，当慢性饮食AlCl₃暴露伴有考来烯胺处理时，与考来烯胺处理时测量的TMA - DPH和DPH各向异性值相比，铝诱导的膜有序性降低可忽略不计。相反，用AlCl₃对突触体（从对照大鼠分离）进行体外孵育会导致这个更亲水的膜区域出现浓度依赖性的刚性化。在体内和体外实验中，铝对突触体膜流动性的相反作用似乎可以通过突触体CH/PL摩尔比的改变来解释，因为在体内暴露于铝期间，该参数会显著降低（约80%）。总之，在体内暴露于铝期间，亲水区的流化和突触前膜CH/PL摩尔比的降低伴随着这种阳离子的积累，这似乎限制了铝在脑皮质神经末梢中的保留。
