Characterization of heterotopic cell clusters in the hippocampus of rats exposed to methylazoxymethanol in utero
Characterization of heterotopic cell clusters in the hippocampus of rats exposed to methylazoxymethanol in utero
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DOI：
10.1016/s0920-1211(99)00104-7
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发表时间：
2000-04-01
影响因子：
2.2
通讯作者：
Schwartzkroin, PA
中科院分区：
文献类型：
--
作者：
Baraban, SC;Wenzel, HJ;Schwartzkroin, PA
皮质紊乱是许多难治性癫痫患儿的主要临床表现之一。为了研究癫痫发作倾向和异常皮质结构之间的关系，我们已经开始表征表现出异常神经元簇（异位症）和皮质分层破坏的动物模型。在这个模型中，将大鼠在子宫内暴露于DNA甲基化剂甲基偶氮甲醇乙酸酯（MAM;胚胎第15天），破坏了正常大脑发育的顺序。在MAM暴露的大鼠中，海马异位的细胞表现出神经元形态，并且不与神经胶质的免疫组织化学标记染色。在MAM暴露动物的海马切片中，异位内的胞外场记录表明，这些发育不良的细胞簇在局部（即在CA 1海马子区域内）形成突触连接，并且还与新皮质细胞形成异常突触接触。切片灌注荷包牡丹碱或4-氨基吡啶导致癫痫样活动的发育不良细胞簇，可以发生独立的输入从CA 3。两者合计，我们的研究结果表明，海马组织异常的区域内的神经元能够独立的癫痫样活动的产生，并可以项目异常放电到新皮层的广泛区域，以及海马。(C)2000 Elsevier Science B. V.保留所有权利。
Cortical disorganization represents one of the major clinical findings in many children with medically intractable epilepsy. To study the relationship between seizure propensity and abnormal cortical structure, we have begun to characterize an animal model exhibiting aberrant neuronal clusters (heterotopia) and disruption of cortical lamination. In this model, exposing rats in utero to the DNA methylating agent methylazoxymethanol acetate (MAM; embryonic day 15) disrupts the sequence of normal brain development. In MAM-exposed rats, cells in hippocampal heterotopia exhibit neuronal morphology and do not stain with immunohistochemical markers for glia. In hippocampal slices from MAM-exposed animals, extracellular field recordings within heterotopia suggest that these dysplastic cell clusters make synaptic connections locally (i.e. within the CA1 hippocampal subregion) and also make aberrant synaptic contact with neocortical cells. Slice perfusion with bicuculline or 4-aminopyridine leads to epileptiform activity in dysplastic cell clusters that can occur independent of input from CA3. Taken together, our findings suggest that neurons within regions of abnormal hippocampal organization are capable of independent epileptiform activity generation, and can project abnormal discharge to a broad area of neocortex, as well as hippocampus. (C) 2000 Elsevier Science B.V. All rights reserved.