Binaschi Anna, Bregola Gianni, Simonato Michele
Department of Clinical and Experimental Medicine, Section of Pharmacology, and Neuroscience Center, University of Ferrara, Ferrara, Italy.
Rev Neurosci. 2003;14(3):285-301. doi: 10.1515/revneuro.2003.14.3.285.
The role of the hippocampal somatostatin (somatotropin release-inhibiting factor, SRIF) system in the control of partial complex seizures is discussed in this review. The SRIF system plays a role in the inhibitory modulation of hippocampal circuitries under normal conditions: 1) SRIF neurons in the dentate gyrus are part of a negative feedback circuit modulating the firing rate of granule cells; 2) SRIF released in CA3 interacts both with presynaptic receptors located on associational/commissural terminals and with postsynaptic receptors located on pyramidal cell dendrites, reducing excitability of pyramidal neurons; 3) in CA1, SRIF exerts a feedback inhibition and reduces the excitatory drive on pyramidal neurons. Significant changes in the hippocampal SRIF system have been documented in experimental models of temporal lobe epilepsy (TLE), in particular in the kindling and in the kainate models. SRIF biosynthesis and release are increased in the kindled hippocampus, especially in the dentate gyrus. This hyper-function may be instrumental to control the latent hyperexcitability of the kindled brain, preventing excessive discharge of the principal neurons and the occurrence of spontaneous seizures. In contrast, the hippocampal SRIF system undergoes damage in the dentate gyrus following kainate-induced status epilepticus. Although surviving SRIF neurons appear to hyperfunction, the loss of hilar SRIF interneurons may compromise inhibitory mechanisms in the dentate gyrus, facilitating the occurrence of spontaneous seizures. In keeping with these data, pharmacological activation of SRIF1 (sst2) receptors, i.e. of the prominent receptor subtype on granule cells, exerts antiseizure effects. Taken together, the data presented suggest that the hippocampal SRIF system plays a role in the control of partial complex seizures and, therefore, that it may be proposed as a therapeutic target for TLE.
本综述讨论了海马生长抑素（促生长激素释放抑制因子，SRIF）系统在部分性复杂性癫痫控制中的作用。在正常情况下，SRIF系统在海马回路的抑制性调节中发挥作用：1）齿状回中的SRIF神经元是调节颗粒细胞放电频率的负反馈回路的一部分；2）在CA3区释放的SRIF与位于联合/连合终末的突触前受体以及位于锥体细胞树突上的突触后受体相互作用，降低锥体细胞的兴奋性；3）在CA1区，SRIF发挥反馈抑制作用，降低对锥体细胞的兴奋性驱动。在颞叶癫痫（TLE）的实验模型中，特别是在点燃模型和谷氨酸钾模型中，已记录到海马SRIF系统的显著变化。在点燃的海马中，尤其是在齿状回中，SRIF的生物合成和释放增加。这种功能亢进可能有助于控制点燃脑的潜在兴奋性过高，防止主要神经元过度放电和自发性癫痫发作的发生。相比之下，在谷氨酸钾诱导的癫痫持续状态后，海马SRIF系统在齿状回中受到损伤。尽管存活的SRIF神经元似乎功能亢进，但门区SRIF中间神经元的丧失可能会损害齿状回中的抑制机制，促进自发性癫痫发作的发生。与这些数据一致，SRIF1（sst2）受体（即颗粒细胞上的主要受体亚型）的药理学激活具有抗癫痫作用。综上所述，所呈现的数据表明海马SRIF系统在部分性复杂性癫痫的控制中发挥作用，因此，它可能被提议作为TLE的治疗靶点。
