Paiva Daisyléa de Souza, Romariz Simone Amaro Alves, Valente Maria Fernanda, Moraes Luiz Bruno, Covolan Luciene, Calcagnotto Maria Elisa, Monteiro Longo Beatriz
Laboratório de Neurofisiologia, Universidade Federal de São Paulo - UNIFESP, São Paulo, Brazil.
Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, Brazil.
Epilepsy Behav. 2017 May;70(Pt A):125-130. doi: 10.1016/j.yebeh.2017.03.015. Epub 2017 Apr 17.
Medial ganglionic eminence (MGE) is one of the sources of inhibitory interneurons during development. Following transplantation in postnatal developing brain, MGE cells can increase local inhibition suggesting a possible protection to GABAergic dysfunction in brain disorders, such as epilepsy. Since it has been shown that MGE-derived cells harvested as neurospheres are able to suppress seizures, it might be important to investigate whether these protective effects would change in different seizure models. Here, we used pentylenetetrazole-(PTZ) and maximal electroshock (MES)-induced seizure models to test whether the transplantation of MGE cells would increase the threshold to trigger acute seizures. When transplanted into the neocortex (layers 3-4) of neonatal mice (postnatal days 3-4), MGE cells were able to survive and were mainly found in piriform cortex, fimbria, and ventricular wall regions. Additionally, the number of GFP+ cells found in the brains of mice induced with PTZ and MES differed significantly and suggests proliferation and larger survival rate of MGE-transplanted cells after PTZ, but not MES-induced seizures. Following transplantation, there was a reduction in the number of animals presenting mild and severe seizures induced by PTZ. Furthermore, MGE-cell transplantation was able to increase threshold to seizures induced by PTZ, but was not able to prevent seizure spread induced by MES.
内侧神经节隆起(MGE)是发育过程中抑制性中间神经元的来源之一。在出生后发育中的大脑中移植后,MGE细胞可增强局部抑制作用,提示其可能对癫痫等脑部疾病中的γ-氨基丁酸(GABA)能功能障碍具有保护作用。由于已有研究表明,以神经球形式收获的源自MGE的细胞能够抑制癫痫发作,因此研究这些保护作用在不同癫痫模型中是否会发生变化可能具有重要意义。在此,我们使用戊四氮(PTZ)和最大电休克(MES)诱导的癫痫模型,来测试MGE细胞移植是否会提高触发急性癫痫发作的阈值。当将MGE细胞移植到新生小鼠(出生后3 - 4天)的新皮质(第3 - 4层)时,MGE细胞能够存活,并且主要分布在梨状皮质、伞和脑室壁区域。此外,在PTZ和MES诱导的小鼠大脑中发现的绿色荧光蛋白(GFP)阳性细胞数量存在显著差异,这表明在PTZ诱导而非MES诱导的癫痫发作后,MGE移植细胞的增殖和存活率更高。移植后,由PTZ诱导出现轻度和重度癫痫发作的动物数量有所减少。此外,MGE细胞移植能够提高PTZ诱导癫痫发作的阈值,但无法阻止MES诱导的癫痫发作扩散。