Fiedler J L, Epstein C J, Rapoport S I, Caviedes R, Caviedes P
Departamento de Bioquímica y Química, Facultad de Medicina, Universidad de Chile, Santiago.
Brain Res. 1994 Sep 26;658(1-2):27-32. doi: 10.1016/s0006-8993(09)90006-3.
The trisomy-16 (TS16) mouse is considered to be a model of human trisomy 21 (Down syndrome) because of genetic homology between mouse chromosome 16 and human chromosome 21. We examined cholinergic function of brain and spinal cord tissue and in cultured neurons from TS16 mouse compared with that of age matched controls. Mean acetylcholinesterase activity in both tissue types did not differ between trisomic and control conditions. Acetylcholine (ACh) synthesis, measured as choline O-acetyltratransferase (acetyl-CoA) activity, was reduced to 67% of control in TS16 brain but not in TS16 spinal cord. Steady-state accumulation of ACh precursor, [3H]choline, was measured in primary cell cultures. Steady-state choline uptake was reduced to 35% and to 61% in neurons of TS16 brain and spinal cord, respectively, when compared with controls. Kinetics experiments in TS16 brain cells showed a 50% reduction of the maximal velocity of choline uptake when compared to controls. Further, the ACh release induced by KCl depolarization in TS16 spinal cord neurons did not differ from control neurons but was reduced in TS16 brain neurons. This effect cannot be explained solely by a reduction in ACh synthesis. The results indicate that the TS16 condition in mice significantly modified the cholinergic function in brain, and to a lesser degree in spinal cord, suggesting that the higher gene dosage inherent to the trisomic condition affects cholinergic neurons in different regions of the central nervous system in a differential fashion.
由于小鼠16号染色体与人类21号染色体存在基因同源性，三体16（TS16）小鼠被认为是人类21三体（唐氏综合征）的模型。我们检测了TS16小鼠脑和脊髓组织以及培养神经元中的胆碱能功能，并与年龄匹配的对照小鼠进行比较。在三体和对照条件下，两种组织类型中的平均乙酰胆碱酯酶活性没有差异。以胆碱O - 乙酰转移酶（乙酰辅酶A）活性衡量的乙酰胆碱（ACh）合成在TS16小鼠脑中降至对照的67%，但在TS16小鼠脊髓中未降低。在原代细胞培养物中测量了ACh前体[3H]胆碱的稳态积累。与对照相比，TS16小鼠脑和脊髓神经元中的稳态胆碱摄取分别降至35%和61%。TS16脑细胞的动力学实验表明，与对照相比，胆碱摄取的最大速度降低了50%。此外，TS16脊髓神经元中由氯化钾去极化诱导的ACh释放与对照神经元没有差异，但在TS16脑神经元中减少。这种效应不能仅用ACh合成的减少来解释。结果表明，小鼠中的TS16状况显著改变了脑中的胆碱能功能，在脊髓中的改变程度较小，这表明三体状况固有的较高基因剂量以不同方式影响中枢神经系统不同区域的胆碱能神经元。
