Activation of non-neuronal cells within the prenatal developing brain of sheep with neuronal ceroid lipofuscinosis
Activation of non-neuronal cells within the prenatal developing brain of sheep with neuronal ceroid lipofuscinosis
复制标题
DOI：
10.1111/j.1750-3639.2006.00002.x
复制
发表时间：
2006-04-01
期刊：
影响因子：
6.4
通讯作者：
Cooper, Jonathan D.
中科院分区：
文献类型：
--
作者：
Kay, Graham W.;Palmer, David N.;Cooper, Jonathan D.
神经元蜡样脂褐质沉积症（NCL，Batten 病）是儿童致命的遗传性溶酶体贮积病，其特征是失明、癫痫发作和严重的神经变性，但导致这些病理变化的机制仍不清楚。具有类似人类大脑的 CLN6 型绵羊和疾病进展对于研究发病机制具有无价的价值。对这些绵羊的临床前病理学研究表明，仅 12 天龄时，局部神经胶质细胞就被激活，特别是在随后退化的皮质区域。通过从妊娠 60 天开始检查胎儿组织，这一范围得到了扩展。一个显着的特征是出生前 40 天，在大脑皮层发育中的白质中发现反应性星形胶质细胞的存在以及血管周围细胞的肥大和增殖。出生前 20 天，星形胶质细胞的激活在皮质灰质内很明显，并在出生后 12 天仅限于浅层。出生后不久，在上新皮质灰质层中检测到激活的小胶质细胞簇。受影响的绵羊的神经元发育在这些早期阶段没有受到干扰。受影响大脑内非神经元细胞的这种产前激活表明大脑发育过程中发病机制的开始，并且神经胶质细胞激活的有序序列先于神经变性。
The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are fatal inherited lysosomal storage diseases of children characterized by increasing blindness, seizures and profound neurodegeneration but the mechanisms leading to these pathological changes remain unclear. Sheep with a CLN6 form that have a human-like brain and disease progression are invaluable for studying pathogenesis. A study of preclinical pathology in these sheep revealed localized glial activation at only 12 days of age, particularly in cortical regions that subsequently degenerate. This has been extended by examining fetal tissue from 60 days of gestation onwards. A striking feature was the presence of reactive astrocytes and the hypertrophy and proliferation of perivascular cells noted within the developing white matter of the cerebral cortex 40 days before birth. Astrocytic activation was evident within the cortical gray matter 20 days before birth, and was confined to the superficial laminae 12 days after birth. Clusters of activated microglia were detected in upper neocortical gray matter laminae shortly after birth. Neuronal development in affected sheep was undisturbed at these early ages. This prenatal activation of non-neuronal cells within the affected brain indicates the onset of pathogenesis during brain development and that an ordered sequence of glial activation precedes neurodegeneration.