Yawata Izumi, Tanaka Kazuaki, Nakagawa Yukinori, Watanabe Yasuo, Murashima Yoshiya L, Nakano Kiwao
Nagoya University Bioscience and Biotechnology Center, Chikusa, Nagoya 464-8601, Japan.
Brain Res Mol Brain Res. 2004 Dec 6;132(1):13-7. doi: 10.1016/j.molbrainres.2004.08.019.
The EL mouse is an animal model for hereditary temporal lobe epilepsy. When the mice receive weekly vestibular stimulation, e.g., 30 "tosses", 10-15 cm vertically, they start to convulse after 1-2 weeks. The aim of this study was to evaluate the role of the histaminergic neurons in the regulation of seizure development in the EL mice. The obtained results indicated that administration of either histidine, a substrate for histamine synthesis, or metoprine (2,4-diamino-5-(3,4-dichlorophnyl)-6-methyl-pyrimidine), an inhibitor of histamine N-methyltransferase (HNMT), retarded the onset of seizure episodes in the mice. The co-administration of histidine and metoprine caused a more marked delay in it. The histamine levels in the brain significantly increased in response to any of these treatments. The intraperitoneal injection of diphenhydramine, a H1-antagonist accelerated the initiation of seizure episodes in the mice, whereas thioperamide, a H3-antagonist caused a delay in the response. There were significant increases in the brain histamine levels upon injection of any of these drugs with concomitant rises in the activity of the histidine decarboxylase (HDC). These results, taken together, suggest that the histaminergic neurons play crucial roles in the development of seizures in the EL mice. They inhibit convulsion in a H1-dependent fashion, while the neurons enhance it in a H3-receptor-mediated way.
EL小鼠是遗传性颞叶癫痫的动物模型。当小鼠每周接受前庭刺激，例如垂直方向10 - 15厘米的30次“抛掷”时，它们在1 - 2周后开始惊厥。本研究的目的是评估组胺能神经元在EL小鼠癫痫发作发展调节中的作用。所得结果表明，给予组胺合成底物组氨酸或组胺N - 甲基转移酶（HNMT）抑制剂美托普利（2,4 - 二氨基 - 5 -（3,4 - 二氯苯基）- 6 - 甲基嘧啶），可延缓小鼠癫痫发作的起始。组氨酸和美托普利联合给药导致更显著的延迟。对这些处理中的任何一种反应时，脑内组胺水平显著升高。腹腔注射H1拮抗剂苯海拉明加速了小鼠癫痫发作的起始，而H3拮抗剂硫代酰胺则导致反应延迟。注射这些药物中的任何一种后，脑内组胺水平显著升高，同时组氨酸脱羧酶（HDC）活性也升高。综合这些结果表明，组胺能神经元在EL小鼠癫痫发作发展中起关键作用。它们以H1依赖的方式抑制惊厥，而神经元以H3受体介导的方式增强惊厥。
