Sadegh M, Mirnajafi-Zadeh J, Javan M, Fathollahi Y, Mohammad-Zadeh M, Jahanshahi A, Noorbakhsh S M
Department of Physiology, School of Medical Sciences, Tarbiat Modares University, PO Box 14115-111, Tehran, IR. Iran.
Neuroscience. 2007 Dec 5;150(2):396-403. doi: 10.1016/j.neuroscience.2007.09.068. Epub 2007 Oct 9.
Low-frequency stimulation (LFS) has antiepileptogenic effects on kindled seizures. In the present study, the role of galanin receptors in the inhibitory effect of LFS on perforant path kindling acquisition was investigated in rats. Animals were kindled by perforant path stimulation in a rapid kindling manner (six stimulations per day). LFS (0.1 ms pulses at 1 Hz, 600 pulses, and 80-150 microA) was applied immediately after termination of each kindling stimulation. M35 (0.5 and 1.0 nM per site), a nonselective galanin receptor antagonist and M871 (1.0 microM per site), a selective galanin receptor type 2 (GalR2) antagonist, were daily microinjected into the dentate gyrus before starting the stimulation protocol. The expression of GalR2 in the dentate gyrus was also investigated using semi-quantitative RT-PCR. Application of LFS significantly retarded the kindling acquisition and delayed the expression of different kindled seizure stages. In addition, LFS significantly reduced the increment of daily afterdischarge duration during kindling development. Intra-dentate gyrus microinjection of both M35 and M871 significantly prevented the inhibitory effects of LFS on kindling parameters. During the focal kindled seizure stages (1-3) M871 had no significant effect. However, during generalized seizure stages (4 and 5), M871 had the same effect as M35. Semi-quantitative RT-PCR also showed that after kindling acquisition, the GalR2 mRNA level decreased in the dentate gyrus but application of LFS prevented this decrease. Obtained results show that activation of galanin receptors by endogenous galanin has a role in mediating the inhibitory effect of LFS on perforant path-kindled seizures. This role is exerted through GalR1 during focal- and through GalR2 during generalized-kindled seizures.
低频刺激（LFS）对点燃性癫痫发作具有抗癫痫发生作用。在本研究中，探讨了甘丙肽受体在LFS对穿通通路点燃获得的抑制作用中的作用，实验对象为大鼠。通过快速点燃方式（每天6次刺激）对动物进行穿通通路刺激以使其点燃。在每次点燃刺激结束后立即施加LFS（1Hz、0.1ms脉冲、600个脉冲、80 - 150微安）。在开始刺激方案前，每天将非选择性甘丙肽受体拮抗剂M35（每部位0.5和1.0纳摩尔）和选择性甘丙肽2型受体（GalR2）拮抗剂M871（每部位1.0微摩尔）微量注射到齿状回中。还使用半定量逆转录聚合酶链反应（RT-PCR）研究了齿状回中GalR2的表达。施加LFS显著延缓了点燃获得过程，并延迟了不同点燃癫痫发作阶段的出现。此外，LFS显著降低了点燃发展过程中每日放电后持续时间的增加。向齿状回内微量注射M35和M871均显著阻止了LFS对点燃参数的抑制作用。在局灶性点燃癫痫发作阶段（1 - 3），M871没有显著作用。然而，在全身性癫痫发作阶段（4和5），M871与M35具有相同的作用。半定量RT-PCR还显示，在点燃获得后，齿状回中GalR2 mRNA水平下降，但施加LFS可阻止这种下降。所得结果表明，内源性甘丙肽激活甘丙肽受体在介导LFS对穿通通路点燃性癫痫发作的抑制作用中发挥作用。这种作用在局灶性癫痫发作时通过GalR1发挥，在全身性癫痫发作时通过GalR2发挥。
