Departamento de Ciencias Médicas, Universidad de Castilla-La Mancha, Albacete, Spain.
J Neurosci Res. 2010 Jan;88(1):155-66. doi: 10.1002/jnr.22177.
The early-onset, irreversible, severe deficits of learning and memory in the senescence-accelerated mouse (SAM)-prone/8 (SAMP8) support its use as an animal model for human dementias of early onset. Possible implication of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in cognitive dysfunction of SAMP8 mice was studied by comparing cholinesterase (ChE) expression in brains of SAMP8 mice and of their normal control, SAM-resistant/1 (SAMR1) mice. The level of ChE mRNAs was the same in SAMP8 and SAMR1 brains, which agreed with their equal AChE activity (3.09 +/- 1.45 vs. 3.07 +/- 1.44 mumol.hr(-1).mg protein(-1), U/mg), but not with a doubled BuChE activity in SAMP8 brain (0.14 +/- 0.05 vs. 0.07 +/- 0.02 U/mg; P < 0.01). This great increase in neural BuChE activity may contribute to cognitive deficit of SAMP8 mice. Hydrophilic (G(4) (H), 8%) and amphiphilic (G(4) (A), 74%) AChE tetramers, besides dimers and monomers (G(2) (A) + G(1) (A), 18%), were identified in SAMR1 brains. They also contained G(4) (H) BuChE forms (18%) as well as G(4) (A) (53%) and G(2) (A) + G(1) (A) (29%) species. Although SAMP8 brain displayed proportions of AChE and BuChE forms that were similar to those of SAMR1 brain, phenyl-agarose chromatography with detergent-free extracts showed a rise in the proportion of secretory G(4) (H) BuChE from 35% in SAMR1 to 44% in SAMP8 brain. The strong immunolabelling of glial fibrillary acidic protein (GFAP), a marker of reactive gliosis, in SAMP8 brain and the consideration of BuChE as a marker of glial cells suggest a relationship between phenotypic changes in neuroglial cells and the excess of BuChE activity in SAMP8 brain.
早发性、不可逆转、严重的学习和记忆缺陷加速了衰老小鼠（SAM- 易发生/8 型）（SAMP8）的发生，使其成为人类早发性痴呆动物模型。通过比较 SAMP8 小鼠和正常对照 SAM 抗性/1 型（SAMR1）小鼠大脑中的胆碱酯酶（ChE）表达，研究了乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）在 SAMP8 小鼠认知功能障碍中的可能作用。SAMP8 和 SAMR1 大脑中的 ChE mRNA 水平相同，这与它们相等的 AChE 活性（3.09 +/- 1.45 vs. 3.07 +/- 1.44 mumol.hr(-1).mg protein(-1)，U/mg）一致，但 SAMP8 大脑中的 BuChE 活性增加了一倍（0.14 +/- 0.05 vs. 0.07 +/- 0.02 U/mg；P < 0.01）。这种神经 BuChE 活性的大幅增加可能导致 SAMP8 小鼠的认知缺陷。在 SAMR1 大脑中，除了二聚体和单体（G(2) (A) + G(1) (A)，18%）外，还鉴定出亲水性（G(4) (H)，8%）和两亲性（G(4) (A)，74%）AChE 四聚体。它们还含有 G(4) (H) BuChE 形式（18%）以及 G(4) (A)（53%）和 G(2) (A) + G(1) (A)（29%）。尽管 SAMP8 大脑中 AChE 和 BuChE 形式的比例与 SAMR1 大脑相似，但用无去污剂提取物进行苯琼脂糖层析显示，分泌型 G(4) (H) BuChE 的比例从 SAMR1 的 35%上升到 SAMP8 的 44%。SAMP8 大脑中神经胶质纤维酸性蛋白（GFAP）的强烈免疫标记，GFAP 是反应性神经胶质增生的标志物，以及 BuChE 作为神经胶质细胞标志物的考虑，表明神经胶质细胞表型变化与 SAMP8 大脑中 BuChE 活性的增加之间存在关系。
