Colacitti C, Sancini G, Franceschetti S, Cattabeni F, Avanzini G, Spreafico R, Di Luca M, Battaglia G
Department of Neurophysiology, Neurological Institute C. Besta, Milano, Italy.
Epilepsy Res. 1998 Sep;32(1-2):49-62. doi: 10.1016/s0920-1211(98)00039-4.
We are currently investigating various treatments which could determine, in the rat brain, structural abnormalities mimicking those reported in human brain dysgeneses. We can induce the formation of neuronal heterotopia in the progeny of rats by means of a double injection of the cytotoxic agent methylazoxymethanol acetate (MAM) on embryonic day 15. We have now investigated the anatomical connections of these heterotopia by means of anterograde and retrograde tract tracing techniques. The induced heterotopia along the border of the lateral ventricles shared common anatomical features with the periventricular nodules in human periventricular or subcortical nodular heterotopia (PNH). The tract tracing data demonstrated the existence of reciprocal connections between the neuronal heterotopia and the ipsilateral and contralateral cortical areas, and the presence of abnormal cortico-hippocampal and cortico-cortical connections. On the basis of the connectivity patterns, it may be speculated that some cells in the heterotopia could be neurons originally committed to the cortex, that were interrupted in their migration by the MAM treatment. Given the common morphological features seen in human PNH and MAM-induced brain heterotopia, the anatomical and developmental analysis of MAM-treated rats may shed light on the mechanisms by which human brain dysgeneses develop in human patients.
我们目前正在研究各种治疗方法，这些方法可能会在大鼠脑中确定模仿人类脑发育异常所报道的结构异常。我们可以通过在胚胎第15天双次注射细胞毒性剂乙酸甲基偶氮甲醇（MAM），在大鼠子代中诱导神经元异位形成。我们现在已经通过顺行和逆行束路追踪技术研究了这些异位的解剖连接。沿侧脑室边界诱导的异位与人类脑室周围或皮质下结节性异位症（PNH）中的脑室周围结节具有共同的解剖特征。束路追踪数据表明神经元异位与同侧和对侧皮质区域之间存在相互连接，并且存在异常的皮质 - 海马和皮质 - 皮质连接。根据连接模式，可以推测异位中的一些细胞可能是原本应迁移到皮质的神经元，它们在迁移过程中被MAM治疗中断。鉴于在人类PNH和MAM诱导的脑异位中看到的共同形态特征，对MAM处理的大鼠进行解剖学和发育分析可能会揭示人类患者脑发育异常发生的机制。
