Genetic defects disrupting glial ion and water homeostasis in the brain.
Genetic defects disrupting glial ion and water homeostasis in the brain.
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DOI：
10.1111/bpa.12602
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
van der Knaap MS
中科院分区：
文献类型：
--
作者：
Min R;van der Knaap MS
大脑中神经元的电活动是由细胞内和细胞外区室之间的离子运动引起的，是我们所有思想和行动的基础。因此，保持正确的离子浓度梯度对于大脑功能至关重要。离子通量伴随着渗透压水的置换。由于即使是轻微的脑肿胀也会导致严重的脑损伤甚至死亡，因此必须严格调节脑离子和水的运动。胶质细胞，特别是星形胶质细胞，在离子和水稳态中发挥关键作用。它们具有特定的通道、泵和载体来调节离子和水流。神经胶质细胞形成一个大的神经胶质合胞体，以帮助吸收和分散离子和水，并与脑液屏障广泛接触，以处理多余的离子和水。参与离子和水稳态的神经胶质蛋白的遗传缺陷会破坏大脑功能，从而导致神经系统疾病。由于白质水肿通常是疾病的标志性特征，因此许多这些疾病的特征是脑白质营养不良。在这篇综述中，我们通过整合 MRI、遗传学、神经病理学和疾病动物模型的发现，总结了目前对以脑离子和水稳态紊乱为特征的遗传性神经胶质疾病的理解。我们讨论不同神经胶质蛋白的突变如何导致疾病，并强调这些疾病之间的异同。为了对这类疾病进行有效的治疗，更好地了解神经胶质细胞如何塑造大脑中离子和水的运动至关重要。
Electrical activity of neurons in the brain, caused by the movement of ions between intracellular and extracellular compartments, is the basis of all our thoughts and actions. Maintaining the correct ionic concentration gradients is therefore crucial for brain functioning. Ion fluxes are accompanied by the displacement of osmotically obliged water. Since even minor brain swelling leads to severe brain damage and even death, brain ion and water movement has to be tightly regulated. Glial cells, in particular astrocytes, play a key role in ion and water homeostasis. They are endowed with specific channels, pumps and carriers to regulate ion and water flow. Glial cells form a large panglial syncytium to aid the uptake and dispersal of ions and water, and make extensive contacts with brain fluid barriers for disposal of excess ions and water. Genetic defects in glial proteins involved in ion and water homeostasis disrupt brain functioning, thereby leading to neurological diseases. Since white matter edema is often a hallmark disease feature, many of these diseases are characterized as leukodystrophies. In this review we summarize our current understanding of inherited glial diseases characterized by disturbed brain ion and water homeostasis by integrating findings from MRI, genetics, neuropathology and animal models for disease. We discuss how mutations in different glial proteins lead to disease, and highlight the similarities and differences between these diseases. To come to effective therapies for this group of diseases, a better mechanistic understanding of how glial cells shape ion and water movement in the brain is crucial.
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