基因敲除小鼠揭示了神经肽Y的关键抗癫痫作用。
Knock-out mice reveal a critical antiepileptic role for neuropeptide Y.
作者信息
Baraban S C, Hollopeter G, Erickson J C, Schwartzkroin P A, Palmiter R D
机构信息
Department of Neurological Surgery, Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.
出版信息
J Neurosci. 1997 Dec 1;17(23):8927-36. doi: 10.1523/JNEUROSCI.17-23-08927.1997.
Abstract
Neuropeptide Y (NPY) inhibits excitatory synaptic transmission in the hippocampus and is implicated in control of limbic seizures. In the present study, we examined hippocampal function and the response to pharmacologically induced seizures in mutant mice lacking this peptide. In slice electrophysiology studies, no change in normal hippocampal function was observed in NPY-deficient mice compared with normal wild-type littermates. Kainic acid (KA) produced limbic seizures at a comparable latency and concentration in NPY-deficient mice compared with littermates. However, KA-induced seizures progressed uncontrollably and ultimately produced death in 93% of NPY-deficient mice, whereas death was rarely observed in wild-type littermates. Intracerebroventricular NPY infusion, before KA administration, prevented death in NPY-deficient mice. These results suggest a critical role for endogenous NPY in seizure control.
摘要
神经肽Y（NPY）可抑制海马体中的兴奋性突触传递，并与边缘性癫痫的控制有关。在本研究中，我们检测了缺乏这种肽的突变小鼠的海马体功能以及对药物诱发癫痫的反应。在脑片电生理研究中，与正常野生型同窝小鼠相比，NPY缺陷小鼠的正常海马体功能未观察到变化。与同窝小鼠相比，NPY缺陷小鼠中， kainic acid（KA）在相当的潜伏期和浓度下引发了边缘性癫痫。然而，KA诱发的癫痫在NPY缺陷小鼠中无法控制地进展，最终导致93%的NPY缺陷小鼠死亡，而在野生型同窝小鼠中很少观察到死亡。在给予KA之前，脑室内注入NPY可防止NPY缺陷小鼠死亡。这些结果表明内源性NPY在癫痫控制中起关键作用。
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本文引用的文献
1
Life without neuropeptide Y.没有神经肽Y的生活。
Recent Prog Horm Res. 1998;53:163-99.
2
Powerful inhibition of kainic acid seizures by neuropeptide Y via Y5-like receptors.神经肽Y通过Y5样受体对海人酸诱发的癫痫发作具有强大的抑制作用。
Nat Med. 1997 Jul;3(7):761-4. doi: 10.1038/nm0797-761.
3
Effects of prenatal cocaine exposure on the developing hippocampus: intrinsic and synaptic physiology.产前可卡因暴露对发育中海马体的影响：内在和突触生理学。
J Neurophysiol. 1997 Jan;77(1):126-36. doi: 10.1152/jn.1997.77.1.126.
4
Release of peptide cotransmitters in Aplysia: regulation and functional implications.海兔中肽类共递质的释放：调节及其功能意义
J Neurosci. 1996 Dec 15;16(24):8105-14. doi: 10.1523/JNEUROSCI.16-24-08105.1996.
5
Update on the mechanism of action of antiepileptic drugs.抗癫痫药物作用机制的最新进展。
Epilepsia. 1996;37 Suppl 6:S4-11. doi: 10.1111/j.1528-1157.1996.tb06038.x.
6
Neuropeptide Y inhibits hippocampal seizures and wet dog shakes.神经肽Y可抑制海马体癫痫发作和湿狗样抖动。
Brain Res. 1996 Oct 21;737(1-2):162-8. doi: 10.1016/0006-8993(96)00730-5.
7
Inhibitory effect of NPY on the picrotoxin-induced activity in the hippocampus: a behavioural and electrophysiological study.神经肽Y对海马中印防己毒素诱导活性的抑制作用：一项行为学和电生理学研究。
Neuropeptides. 1996 Feb;30(1):7-12. doi: 10.1016/s0143-4179(96)90048-7.
8
Inhibitory effect of neuropeptide y on epileptiform activity in the frontal cortex and hippocampus in vitro.神经肽Y对体外培养的额叶皮质和海马癫痫样活动的抑制作用。
Pol J Pharmacol. 1995 Sep-Oct;47(5):461-3.
9
Selective upregulation of T alpha 1 alpha-tubulin and neuropeptide Y mRNAs after intermittent excitatory stimulation in adult rat hippocampus in vivo.成年大鼠海马体在体间歇性兴奋性刺激后Tα1α-微管蛋白和神经肽Y mRNA的选择性上调
J Comp Neurol. 1996 Mar 25;367(1):132-46. doi: 10.1002/cne.903670102.
10
Autoradiographic analysis of neuropeptide Y receptor binding sites in the rat hippocampus after kainic acid-induced limbic seizures.海藻酸诱导边缘叶癫痫发作后大鼠海马中神经肽Y受体结合位点的放射自显影分析
Neuroscience. 1996 Jan;70(1):47-55. doi: 10.1016/0306-4522(95)00332-d.
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