Department of Cell Biology, University of Valencia, Dr Moliner Street, 50, 46100 Burjassot, Valencia, Spain.
J Neural Transm (Vienna). 2010 Apr;117(4):445-55. doi: 10.1007/s00702-010-0376-9. Epub 2010 Feb 16.
Down's syndrome (DS), with an incidence of one in 800 live births, is the most common genetic disorder associated with mental retardation. This trisomy on chromosome 21 induces a variable phenotype in which the only common feature is the presence of mental retardation. The neural mechanisms underlying mental retardation might include defects in the formation of neuronal networks and neural plasticity. DS patients have alterations in the morphology, the density and the distribution of dendritic spines in the pyramidal neurons of the cortex. Our hypothesis is that the deficits in dendritic arborization observed in the principal neurons of DS patients and Ts65Dn mice (a model for DS that mimics most of the structural alterations observed in humans) may be mediated to some extent by changes in their inhibitory inputs. Different types of interneurons control different types of inhibition. Therefore, to understand well the changes in inhibition in DS, it is necessary to study the different types of interneurons separately. We have studied the expression of synaptophysin, Glutamic acid decarboxylase-67 (GAD-67) and calcium-binding protein-expressing cells in the primary somatosensory cortex of 4-5 month old Ts65Dn mice. We have observed an increment of GAD67 immunoreactivity that is related mainly to an increment of calretinin-immunoreactive cells and among them the ones with bipolar morphology. Since there is a propensity for epilepsy in DS patients, this increase in interneurons might reflect an attempt by the system to block overexcitation rather than an increment in total inhibition and could explain the deficit in interneurons and principal cells observed in elderly DS patients.
唐氏综合征（DS）的发病率为每 800 例活产儿中有 1 例，是最常见的与智力障碍相关的遗传疾病。21 号染色体的三体导致了一种可变的表型，其中唯一的共同特征是智力障碍的存在。智力障碍的神经机制可能包括神经元网络形成和神经可塑性的缺陷。DS 患者的皮质锥体神经元中的树突棘形态、密度和分布发生改变。我们的假设是，在 DS 患者和 Ts65Dn 小鼠（一种模拟人类观察到的大多数结构改变的 DS 模型）的主要神经元中观察到的树突分支缺陷可能在某种程度上是由其抑制性输入的变化介导的。不同类型的中间神经元控制不同类型的抑制。因此，要很好地理解 DS 中的抑制变化，有必要分别研究不同类型的中间神经元。我们研究了 4-5 月龄 Ts65Dn 小鼠初级体感皮层中突触小体蛋白、谷氨酸脱羧酶-67（GAD-67）和钙结合蛋白表达细胞的表达。我们观察到 GAD67 免疫反应性增加，主要与钙调蛋白免疫反应性细胞增加有关，其中包括双极形态的细胞。由于 DS 患者有癫痫发作的倾向，中间神经元的这种增加可能反映了系统试图阻止过度兴奋，而不是总抑制的增加，这可以解释老年 DS 患者中观察到的中间神经元和主要细胞的缺失。
