Herberg L J, Rose I C, de Belleroche J S, Mintz M
Experimental Psychology Laboratory, Institute of Neurology, London, UK.
Epilepsy Res. 1992 Mar;11(1):3-7. doi: 10.1016/0920-1211(92)90015-l.
It has been suggested that the kindling of seizures may depend on the induction of genes encoding enzymes involved in neurotransmission. Experimental seizures are followed by an especially rapid and massive induction of brain ornithine decarboxylase (ODC), an enzyme which catalyses the rate-limiting step in the synthesis of polyamines. The latter compounds have been shown to act as positive allosteric modulators of the NMDA receptor, and also to play an important role in cell growth and differentiation. The induction of ODC by seizures has accordingly been suggested to play a pivotal role in the changes in synaptic structure and function that underlie kindling. In the present study we examined the progress of kindling during treatment with alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC. We found that progressive increase in the duration and severity of kindled seizures and in the duration of local afterdischarges was unaffected by daily injections of DFMO in doses previously shown to cause substantial depression of brain ODC activity. Treatment with DFMO also failed to produce significant anticonvulsant or proconvulsant effects. Progressive increase in seizure activity during kindling is therefore unlikely to depend to any appreciable extent on enhanced synthesis of polyamines by ODC.
有人提出，癫痫发作的点燃可能取决于编码参与神经传递的酶的基因的诱导。实验性癫痫发作后，脑鸟氨酸脱羧酶（ODC）会迅速大量诱导，该酶催化多胺合成中的限速步骤。后一种化合物已被证明可作为NMDA受体的正变构调节剂，并且在细胞生长和分化中也起重要作用。因此，有人认为癫痫发作诱导ODC在点燃基础的突触结构和功能变化中起关键作用。在本研究中，我们研究了用α-二氟甲基鸟氨酸（DFMO）治疗期间点燃的进展，DFMO是ODC的不可逆抑制剂。我们发现，点燃性癫痫发作的持续时间和严重程度以及局部放电后持续时间的逐渐增加不受每日注射DFMO的影响，先前已证明该剂量会导致脑ODC活性大幅降低。用DFMO治疗也未能产生明显的抗惊厥或惊厥前作用。因此，点燃过程中癫痫发作活动的逐渐增加不太可能在任何可观程度上取决于ODC增强多胺的合成。
