Hunsberger Joshua G, Bennett Alica H, Selvanayagam Emmanuel, Duman Ronald S, Newton Samuel S
Yale University School of Medicine, 34 Park Street, CMHC, New Haven, CT 06520, USA.
Brain Res Mol Brain Res. 2005 Nov 18;141(1):95-112. doi: 10.1016/j.molbrainres.2005.08.005. Epub 2005 Sep 13.
Kainic acid activates non-N-methyl-d-aspartate (NMDA) glutamate receptors where it increases synaptic activity resulting in seizures, neurodegeneration, and remodeling. We performed microarray analysis on rat hippocampal tissue following kainic acid treatment in order to study the signaling mechanisms underlying these diverse processes in an attempt to increase our current understanding of mechanisms contributing to such fundamental processes as neuronal protection and neuronal plasticity. The kainic acid-treated rats used in our array experiments demonstrated severe seizure behavior that was also accompanied by neuronal degeneration which is suggested by fluoro-jade B staining and anti-caspase-3 immunohistochemistry. The gene profile revealed 36 novel kainic acid regulated genes along with additional genes previously reported. The functional roles of these novel genes are discussed. These genes mainly have roles in transcription and to a lesser extent have roles in cell death, extracellular matrix remodeling, cell cycle progression, neuroprotection, angiogenesis, and synaptic signaling. Gene regulation was confirmed via quantitative real time polymerase chain reaction and in situ hybridization.
海藻酸激活非 N-甲基-D-天冬氨酸(NMDA)谷氨酸受体,增加突触活性,导致癫痫发作、神经退行性变和重塑。我们对海藻酸处理后的大鼠海马组织进行了微阵列分析,以研究这些不同过程背后的信号传导机制,试图加深我们目前对神经元保护和神经元可塑性等基本过程的机制的理解。我们阵列实验中使用的经海藻酸处理的大鼠表现出严重的癫痫行为,同时伴有神经元变性,这通过氟玉 B 染色和抗半胱天冬酶-3 免疫组织化学得以证实。基因谱揭示了 36 个新的海藻酸调节基因以及先前报道的其他基因。讨论了这些新基因的功能作用。这些基因主要在转录中发挥作用,在细胞死亡、细胞外基质重塑、细胞周期进程、神经保护、血管生成和突触信号传导中发挥的作用较小。通过定量实时聚合酶链反应和原位杂交证实了基因调控。