SINGLE MOSSY FIBER AXONAL SYSTEMS OF HUMAN DENTATE GRANULE CELLS STUDIED IN HIPPOCAMPAL SLICES FROM PATIENTS WITH TEMPORAL-LOBE EPILEPSY
SINGLE MOSSY FIBER AXONAL SYSTEMS OF HUMAN DENTATE GRANULE CELLS STUDIED IN HIPPOCAMPAL SLICES FROM PATIENTS WITH TEMPORAL-LOBE EPILEPSY
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DOI：
10.1523/jneurosci.13-04-01511.1993
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发表时间：
1993-04-01
影响因子：
5.3
通讯作者：
ENGEL, J
中科院分区：
文献类型：
--
作者：
ISOKAWA, M;LEVESQUE, MF;ENGEL, J
先前的组织学和免疫细胞化学研究表明，齿状颗粒细胞轴突（苔藓纤维）的重组可能发生在癫痫人类海马体中（Sutula 等人，1989；Houser 等人，1990；Babb 等人，1991）和癫痫动物模型（Tauck 和 Nadler，1985；Sutula 等人，1988；Sutula 等人，1988；Babb 等人，1991）。克罗宁等人， 1992）。然而，重组轴突的轨迹和形态的神经解剖学分析尚不可用。本研究旨在研究人类癫痫海马中的单齿状颗粒细胞轴突系统。通过将示踪剂（生物细胞素或荧光黄）注入细胞内，将单个苔藓纤维直接可视化到海马切片中，该海马切片是通过手术从患者身上摘下的颞叶制备的，用于治疗顽固性癫痫。确定了两种主要的树枝化模式：（1）亲代轴突延伸至门并穿过门向 CA3 延伸，沿其路径在门中留下侧枝（N = 19 个神经元）； (2)除了上述轴突系统外，在体细胞附近从母体轴突分支出侧枝，投射到颗粒细胞层和分子层，形成异常的轴突通路(N = 9个神经元)。这些异常的侧支具有类似于肺门轴突的大纽扣，并在颗粒细胞层和/或分子层中形成广泛的神经丛。颗粒/分子层络脉总长度平均为1110.8μm，是苔藓纤维总长度（平均3698.5μm）的四分之一。具有异常络脉的神经元的体细胞大小显着大于没有这种络脉的神经元（p < 0.025）。在四个病例中，轴突小丘和亲代轴突近端部分附近存在丝状足状细突，这表明异常的侧支形成可能是这些组织中持续的过程。由于缺乏正常活体人类海马体的对照切片，因此很难评估目前的发现与癫痫的相关程度。然而，与非癫痫性尸检材料相比，蒂姆氏染色和/或强啡肽免疫组织化学证实了本研究中使用的海马体中存在异常苔藓纤维络脉，表明其与癫痫的关系（Babb等，1991，1992）。目前，似乎有一个共识，即苔藓纤维侧枝投射到颗粒上层在正常大鼠（Lorento de No，1934；Claiborne 等人，1986；Seress 等人，1991；本研究）、正常猴子（Seress 等人，1991）和正常人（Houser 等人，1990）中很少发生。因此，我们认为，此处报告的颗粒上层中细胞内染色的异常轴突侧支可能代表与医学上难治性颞叶癫痫相关的重组苔藓纤维的轨迹。
Previous histological and immunocytochemical studies suggest that reorganization of the dentate granule cell axons, the mossy fibers, can occur in epileptic human hippocampus (Sutula et al., 1989; Houser et al., 1990; Babb et al., 1991) and in animal models of epilepsy (Tauck and Nadler, 1985; Sutula et al., 1988; Cronin et al., 1992). However, neuroanatomical analyses of the trajectory and morphology of reorganized axons are not yet available. The present study was conducted to investigate single dentate granule cell axonal systems in human epileptic hippocampus. Individual mossy fibers were directly visualized by injecting a tracer (biocytin or Lucifer yellow) intracellularly in hippocampal slices prepared from temporal lobes that were surgically removed from patients for treatment of intractable epilepsy. Two major arborization patterns were identified: (1) the parent axons extended to and coursed through the hilus toward CA3, leaving collaterals along their paths in the hilus (N = 19 neurons); (2) in addition to the aforementioned axonal system, collateral(s) branched f rom the parent axon near the soma and projected to the granule cell layer and molecular layer, forming an aberrant axonal pathway (N = 9 neurons). These aberrant collaterals bore large boutons similar to those of the hilar axons and formed extensive plexuses in the granule cell layer and/or in the molecular layer. The summed length of collaterals in the granular/molecular layers was 1110.8 mum on average, which was one-fourth of the total summed length of the mossy fibers (3698.5 mum on average). The size of the somata in neurons that had aberrant collaterals was significantly larger than that of neurons without such collaterals (p < 0.025). In four cases, filopodium-like fine processes were present near the axon hillock and proximal parts of the parent axon, suggesting that the aberrant collateral formation might be an ongoing process in these tissues. The lack of control slices from normal living human hippocampus makes it difficult to assess to what extent the present findings are epilepsy associated. However, the presence of aberrant mossy fiber collaterals in the hippocampi used in the present study has been confirmed by Timm's staining and/or dynorphin immunohistochemistry in comparison with nonepileptic autopsy material, indicating its relation to epilepsy (Babb et al., 1991, 1992). At present, there seems to be a consensus that the projection of mossy fiber collaterals to the supragranular layer is a rare occurrence in normal rats (Lorento de No, 1934; Claiborne et al., 1986; Seress et al., 1991; present study), normal monkeys (Seress et al., 1991), and normal humans (Houser et al., 1990). Thus, we believe that the intracellularly stained aberrant axon collaterals reported here in the supragranular layer likely represent trajectories of reorganized mossy fibers associated with medically intractable temporal lobe epilepsy.