神经肽Y在小鼠海马体中的抗癫痫作用需要Y5受体。

Antiepileptic actions of neuropeptide Y in the mouse hippocampus require Y5 receptors.

作者信息

Baraban Scott C

机构信息

Department of Neurological Surgery, University of California-San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

出版信息

Epilepsia. 2002;43 Suppl 5:9-13. doi: 10.1046/j.1528-1157.43.s.5.13.x.

DOI:10.1046/j.1528-1157.43.s.5.13.x

PMID:12121287

Abstract

PURPOSE

Recent evidence suggests an antiepileptic role for neuropeptide Y (NPY) in the central nervous system. The precise receptor subtypes mediating the inhibitory actions of NPY in the hippocampal formation, however, remain unclear. In vitro studies suggest a role for Y2 receptors in modulating excitatory hippocampal synaptic transmission and epileptiform discharge. In vivo studies implicate Y5 receptors. Here we used pharmacologic tools and Y5-receptor knockout mice to examine the role of Y5 receptors in mediating the antiexcitatory and antiepileptic actions of NPY in the hippocampal formation.

METHODS

Hippocampal slices were obtained from age-matched wild-type (WT; 129 s3/svimj) and Y5-receptor knockout (Y5R KO) mice generated on the same background strain. Extracellular or whole-cell voltage-clamp recordings were obtained in area CA3 pyramidale. Evoked population spikes or excitatory postsynaptic currents were monitored during bath application of NPY, NPY13-36, or human pancreatic polypeptide (hPP). In some slices, zero-magnesium cerebrospinal fluid (CSF) was used to evoke spontaneous epileptiform discharges.

RESULTS

NPY and NPY agonists with preference for either Y2 (NPY13-36) or Y5 (hPP) receptor subtypes caused a significant reduction in population spike and excitatory postsynaptic current (EPSC) amplitudes in slices from WT mice. NPY (and NPY agonists) also suppressed zero-magnesium epileptiform burst discharge in slices from WT mice. In contrast, bath application of NPY, NPY13-36, or hPP had no effect in slices from Y5R KO mice.

CONCLUSIONS

NPY modulates excitatory synaptic transmission and inhibits limbic seizure activity in the mouse hippocampus. The antiepileptic actions of NPY, in the mouse, appear to require activation of hippocampal Y5 receptors.

摘要

目的

近期证据表明神经肽Y（NPY）在中枢神经系统中具有抗癫痫作用。然而，介导NPY在海马结构中抑制作用的确切受体亚型仍不清楚。体外研究表明Y2受体在调节海马兴奋性突触传递和癫痫样放电中起作用。体内研究表明Y5受体也有此作用。在此，我们使用药理学工具和Y5受体基因敲除小鼠来研究Y5受体在介导NPY在海马结构中的抗兴奋和抗癫痫作用中的作用。

方法

从年龄匹配的、在相同背景品系上产生的野生型（WT；129 s3/svimj）和Y5受体基因敲除（Y5R KO）小鼠获取海马切片。在CA3锥体区域进行细胞外或全细胞电压钳记录。在浴用NPY、NPY13 - 36或人胰多肽（hPP）期间监测诱发的群体峰电位或兴奋性突触后电流。在一些切片中，使用无镁脑脊液（CSF）诱发自发性癫痫样放电。

结果

优先作用于Y2（NPY13 - 36）或Y5（hPP）受体亚型的NPY和NPY激动剂使WT小鼠切片中的群体峰电位和兴奋性突触后电流（EPSC）幅度显著降低。NPY（和NPY激动剂）也抑制WT小鼠切片中的无镁癫痫样爆发放电。相比之下，浴用NPY、NPY13 - 36或hPP对Y5R KO小鼠的切片没有影响。