Hippocampal pathology in the human neuronal ceroid-lipofuscinoses: distinct patterns of storage deposition, neurodegeneration and glial activation.
Hippocampal pathology in the human neuronal ceroid-lipofuscinoses: distinct patterns of storage deposition, neurodegeneration and glial activation.
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人类神经元蜡样脂褐质病中的海马病理学：存储沉积、神经变性和神经胶质激活的不同模式。
DOI：
10.1111/j.1750-3639.2004.tb00077.x
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Haltia,Matti
中科院分区：
文献类型：
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作者：
Tyynelä,Jaana;Cooper,JonathanD;Khan,MNadeem;Shemilts,StephenJA;Haltia,Matti
神经元蜡样-脂褐质沉积症（NCL）是一种遗传性溶酶体贮积病，目前分为8种形式（CLN 1-CLN 8）。总的来说，NCL构成了儿童期进行性脑病的最常见组，并表现为视力障碍、精神恶化和严重癫痫发作。尽管最近发现了潜在的疾病基因，但导致NCL中神经变性和癫痫的机制仍然知之甚少。为了调查这些事件，我们研究了存储沉积，神经变性，神经胶质细胞激活的模式与CLN 1，CLN 2，CLN 3，CLN 5和CLN 8患者的海马使用组织化学和免疫组织化学。这些不同形式的NCL在海马中共享不同的神经元变性模式，严重累及CA 2-CA 4区，但相对不累及CA 1区。这种选择性变性模式也在化学鉴定的中间神经元中观察到，其根据表型表现出分级的损失严重程度，其中钙视网膜蛋白阳性中间神经元相对较少。此外，神经胶质细胞活化也具有区域特异性，小胶质细胞活化在神经元损失最大的区域最明显，星形胶质细胞活化在神经元损失不太明显的区域突出。总之，NCL共享一个共同的模式，选择性海马病理学，从颞叶癫痫的大多数所看到的不同。
The neuronal ceroid‐lipofuscinoses (NCLs) are recessively inherited lysosomal storage diseases, currently classified into 8 forms (CLN1‐CLN8). Collectively, the NCLs constitute the most common group of progressive encephalopathies of childhood, and present with visual impairment, psychomotor deterioration and severe seizures. Despite recent identification of the underlying disease genes, the mechanisms leading to neurodegeneration and epilepsy in the NCLs remain poorly understood. To investigate these events, we examined the patterns of storage deposition, neurodegeneration, and glial activation in the hippocampus of patients with CLN1, CLN2, CLN3, CLN5 and CLN8 using histochemistry and immunohistochemistry. These different forms of NCL shared distinct patterns of neuronal degeneration in the hippocampus, with heavy involvement of sectors CA2‐CA4 but relative sparing of CA1. This selective pattern of degeneration was also observed in immunohistochemically identified interneurons, which exhibited a graded severity of loss according to phenotype, with calretinin‐positive interneurons relatively spared. Furthermore, glial activation was also regionally specific, with microglial activation most pronounced in areas of greatest neuronal loss, and astrocyte activation prominent in areas where neuronal loss was less evident. In conclusion, the NCLs share a common pattern of selective hippocampal pathology, distinct from that seen in the majority of temporal lobe epilepsies.