McLin Jessica Pilar, Steward Oswald
Reeve-Irvine Research Center, 1105 Gillespie Neuroscience Research Facility, University of California at Irvine, Irvine, CA 92697-4292, USA.
Eur J Neurosci. 2006 Oct;24(8):2191-202. doi: 10.1111/j.1460-9568.2006.05111.x.
We assessed inbred, outbred and hybrid mouse strains for susceptibility to seizures and neurodegeneration induced by systemic administration of kainic acid (KA). Each strain showed a unique pattern of susceptibility to seizures as assessed by the dose necessary to induce continuous tonic clonic seizures, progression through six seizure levels, the number of mice that failed to satisfy seizure criteria, and seizure-induced mortality. In general, the C57BL/6, ICR, FVB/N, and BALB/c strains were resistant to seizures while the C57BL/10, DBA/2 J, and F1 C57BL/6CBA/J strains were vulnerable. Neuronal cell death was quantified in four subfields of the hippocampus: CA3, the hilus of the dentate gyrus, CA1, and the dentate granule cell layer. Neurodegeneration was also semiquantitatively assessed in other brain regions including the neocortex, striatum, thalamus, hypothalamus and amygdala. Although there was variability in the extent of cell death within strains, there were significant differences in the amount of hippocampal cell death between strains and also different patterns of neurodegeneration in affected brain areas. In general, the C57BL/6, C57BL/10, and F1 C57BL/6CBA/J strains were resistant to neurodegeneration while the FVB/N, ICR and DBA/2 J strains were vulnerable. The BALB/c strain was unique in that neurodegeneration was confined to the hippocampus. Consistent with previous findings, the resistant neurodegeneration phenotype was dominant in an F1 cross of resistant and vulnerable inbred strains. Our results, using a large number of mouse strains, definitively demonstrate that a mouse strain's seizure phenotype is not related to its neurodegeneration phenotype.
我们评估了近交系、远交系和杂交小鼠品系对全身注射海藻酸(KA)诱导的癫痫发作和神经退行性变的易感性。通过诱导持续性强直阵挛性癫痫发作所需的剂量、六个癫痫发作水平的进展、未达到癫痫发作标准的小鼠数量以及癫痫发作诱导的死亡率来评估,每个品系都表现出独特的癫痫发作易感性模式。一般来说,C57BL/6、ICR、FVB/N和BALB/c品系对癫痫发作有抗性,而C57BL/10、DBA/2 J和F1 C57BL/6CBA/J品系则易感性较高。在海马体的四个亚区:CA3、齿状回的门区、CA1和齿状颗粒细胞层中对神经元细胞死亡进行了定量。还对包括新皮层、纹状体、丘脑、下丘脑和杏仁核在内的其他脑区进行了神经退行性变的半定量评估。尽管品系内细胞死亡程度存在差异,但品系间海马体细胞死亡量存在显著差异,且受影响脑区的神经退行性变模式也不同。一般来说,C57BL/6、C57BL/10和F1 C57BL/6CBA/J品系对神经退行性变有抗性,而FVB/N、ICR和DBA/2 J品系则易感性较高。BALB/c品系的独特之处在于神经退行性变仅限于海马体。与先前的研究结果一致,在抗性和易感性近交系的F1杂交中,抗性神经退行性变表型占主导。我们使用大量小鼠品系的研究结果明确表明,小鼠品系的癫痫发作表型与其神经退行性变表型无关。