D-serine mitigates cell loss associated with temporal lobe epilepsy.
D-serine mitigates cell loss associated with temporal lobe epilepsy.
复制标题
D丝氨酸可减轻与颞叶癫痫相关的细胞损失。
DOI：
10.1038/s41467-020-18757-2
复制
发表时间：
2020-10-02
影响因子：
16.6
通讯作者：
Kumar SS
中科院分区：
文献类型：
--
作者：
Beesley S;Sullenberger T;Crotty K;Ailani R;D'Orio C;Evans K;Ogunkunle EO;Roper MG;Kumar SS
颞叶癫痫（TLE）是成人中最常见的耐药性癫痫类型，病因不明。TLE的一个标志是内侧内嗅区（MEA）中第3层神经元的特征性丢失，这是癫痫发作发展的基础。干预的一种方法是通过更好地理解潜在的病理生理机制来防止这些神经元的丢失。在这里，我们表明，神经元和神经胶质细胞一起引起的病理是减轻的氨基酸D-丝氨酸，其水平可能会减少癫痫条件下。在TLE动物模型中，将D-丝氨酸局部给予MEA可减弱该区域的神经元损失，从而预防癫痫发生。此外，用D-丝氨酸治疗减少MEA中的星形胶质细胞计数，改变它们的反应状态，并减弱小胶质细胞向该区域的增殖和/或浸润，从而减少神经炎症的有害后果。由于缺乏减少过度兴奋和神经元损失的化合物，具有抗炎特性，并且被大脑良好耐受，D-丝氨酸，一种内源性氨基酸，作为难治性TLE的治疗剂提供了新的希望。颞叶癫痫（TLE）可能对治疗无反应。在这里，作者表明，用D-丝氨酸治疗减轻TLE并作用于神经元和神经胶质，减少啮齿动物中的神经元损失并减少星形胶质细胞和小胶质细胞增生。
Temporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy in adults, with an unknown etiology. A hallmark of TLE is the characteristic loss of layer 3 neurons in the medial entorhinal area (MEA) that underlies seizure development. One approach to intervention is preventing loss of these neurons through better understanding of underlying pathophysiological mechanisms. Here, we show that both neurons and glia together give rise to the pathology that is mitigated by the amino acid D-serine whose levels are potentially diminished under epileptic conditions. Focal administration of D-serine to the MEA attenuates neuronal loss in this region thereby preventing epileptogenesis in an animal model of TLE. Additionally, treatment with D-serine reduces astrocyte counts in the MEA, alters their reactive status, and attenuates proliferation and/or infiltration of microglia to the region thereby curtailing the deleterious consequences of neuroinflammation. Given the paucity of compounds that reduce hyperexcitability and neuron loss, have anti-inflammatory properties, and are well tolerated by the brain, D-serine, an endogenous amino acid, offers new hope as a therapeutic agent for refractory TLE. Temporal lobe epilepsy (TLE) can be unresponsive to treatment. Here, the authors show that treatment with D-Serine mitigates TLE and acts on neurons and glia, attenuating neuronal loss and reducing astro- and microgliosis in rodents.
登录
查看更多内容
影响因子：
4.8
作者：
Kartvelishvily, Elena;Shleper, Maria;Wolosker, Herman
通讯作者：
Wolosker, Herman
影响因子：
2.5
作者：
Honda, Y;Ishizuka, N
通讯作者：
Ishizuka, N
影响因子：
2.5
作者：
STEWARD, O;SCOVILLE, SA
通讯作者：
SCOVILLE, SA
影响因子：
4.7
作者：
Drexel M;Preidt AP;Sperk G
通讯作者：
Sperk G
影响因子：
5.3
作者：
Bushong, EA;Martone, ME;Ellisman, MH
通讯作者：
Ellisman, MH