Ishikura Nako, Tsunashima Koichi, Watanabe Kei ichiro, Nishimura Tsutomu, Minabe Yoshio, Kato Nobumasa
Division of Cortical Function Disorders, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi, Kodaira, 187-8502, Tokyo, Japan.
Neurosci Res. 2002 Nov;44(3):237-48. doi: 10.1016/s0168-0102(02)00132-3.
Trimethyltin (TMT) is an organic metal known to induce neuronal degeneration in the hippocampus, and abnormal behavior characterized by seizures, increased aggression and memory deficits. We administered TMT to rats and studied the changes of neuropeptide Y (NPY) and somatostatin (SOM) in the hippocampus. Phenobarbital (PB) was administered as an anticonvulsant to assess the effect of seizures on neuropeptide expressions in both dorsal and ventral hippocampus. Histochemically, NPY-immunoreactivity increased 4 days after TMT treatment in the hilus of the hippocampus, then progressively decreased and dropped to a level below control 16 days after TMT treatment. Detection of NPY mRNA by in situ hybridization preceded the detection of NPY by immunohistochemistry. NPY mRNA signals increased in the hilus 2 days after TMT treatment. SOM-immunoreactivity also increased in the hilus of the hippocampus 2 days after TMT treatment, then decreased rapidly to a normal level. Similar changes in SOM mRNA were demonstrated by in situ hybridization. PB treatment significantly inhibited changes of NPY in terms of both immunoreactivity and mRNA expression; however, the same treatment failed to affect changes in SOM expression. This suggests that NPY and SOM act by different mechanisms in TMT-induced neurodegeneration.
三甲基锡(TMT)是一种有机金属,已知其可诱导海马体中的神经元退化,并导致以癫痫发作、攻击性增强和记忆缺陷为特征的异常行为。我们给大鼠施用了TMT,并研究了海马体中神经肽Y(NPY)和生长抑素(SOM)的变化。施用苯巴比妥(PB)作为抗惊厥药,以评估癫痫发作对背侧和腹侧海马体中神经肽表达的影响。组织化学研究表明,TMT处理后4天,海马体门区的NPY免疫反应性增加,随后逐渐下降,并在TMT处理后16天降至低于对照的水平。原位杂交检测NPY mRNA先于免疫组织化学检测NPY。TMT处理后2天,海马体门区的NPY mRNA信号增加。TMT处理后2天,海马体门区的SOM免疫反应性也增加,然后迅速降至正常水平。原位杂交显示SOM mRNA有类似变化。PB处理在免疫反应性和mRNA表达方面均显著抑制了NPY的变化;然而,相同处理未能影响SOM表达的变化。这表明NPY和SOM在TMT诱导的神经退行性变中通过不同机制起作用。