β-estradiol increases dentate gyrus inhibition in female rats via augmentation of hilar neuropeptide Y
β-estradiol increases dentate gyrus inhibition in female rats via augmentation of hilar neuropeptide Y
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DOI：
10.1523/jneurosci.0366-07.2007
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发表时间：
2007-05-30
影响因子：
5.3
通讯作者：
Velisek, Libor
中科院分区：
文献类型：
--
作者：
Veliskova, Jana;Velisek, Libor
齿状回将传入的活动过滤到海马体中。它在学习和记忆以及癫痫等病理状态中发挥作用。齿状回的一些门部中间神经元表达神经肽Y (NPY)，它调节颗粒细胞的活性。表达npy的抑制性中间神经元亚群对癫痫引起的损伤敏感。对去卵巢大鼠进行β -雌二醇预处理可保护肝门间神经元免受癫痫性损伤，包括含有npy的损伤敏感亚群。在这里，我们证明β -雌二醇可以增强肝门间神经元内NPY的表达。混合穿孔路径的体外配对脉冲刺激显示，β -雌二醇诱导的颗粒细胞网络抑制增强，在200 - 300 ms（相当于3 -5 Hz）之间的刺激间隔是NPY敏感的，涉及Y-1受体，而对GABAB或代谢性谷氨酸受体拮抗剂不敏感。此外，β -雌二醇预处理可减弱齿状回低频（3.3或5 Hz）爆发活动的传播。脑室内给予抗NPY抗体清除内源性NPY，与单独使用β -雌二醇处理的大鼠相比，加速了kainic酸诱导的癫痫发作，增加了癫痫引起的脑门神经元损伤。综上所述，我们发现β -雌二醇上调肝门NPY，这导致齿状回对3 - 5hz输入频率的抑制增强。这种频率与某些癫痫患者在发作开始时记录的放电频率相似。因此，β -雌二醇诱导的3 - 5hz频率的npy敏感过滤可能是传入癫痫发作活动的重要调节器，但它也可能在调节流入海马的信息流方面具有生理目的。
The dentate gyrus filters incoming activity into the hippocampus proper. It plays a role in learning and memory and in pathological states such as epilepsy. Some of hilar interneurons of the dentate gyrus express neuropeptide Y (NPY), which modulates granule cell activity. A subpopulation of the NPY-expressing inhibitory interneurons is sensitive to seizure-induced damage. Pretreatment with beta-estradiol in ovariectomized rats protects hilar interneurons against seizure-induced injury, including the NPY-containing damage-sensitive subpopulation. Here, we demonstrate that beta-estradiol enhances NPY expression within the hilar interneurons. In vitro paired-pulse stimulation of the mixed perforant path revealed beta-estradiol-induced augmentation of granule cell network inhibition, which at interstimulus intervals between 200 and 300 ms (corresponding to similar to 3 -5 Hz) was NPY sensitive and involved Y-1 receptors, whereas it was insensitive to GABAB or metabotropic glutamate receptor antagonists. Additionally, beta-estradiol pretreatment attenuated propagation of low-frequency (3.3 or 5 Hz) burst activity through the dentate gyrus. Scavenging endogenous NPY by intracerebroventricular administration of anti-NPY antibody accelerated kainic acid-induced seizure onset and increased seizure-induced neuronal damage in the hilus compared with rats treated with beta-estradiol alone. Together, we show that beta-estradiol upregulates hilar NPY and that this leads to enhancement in dentate gyrus inhibition of incoming frequencies between 3 and 5 Hz. Such frequencies are similar to the discharge frequencies recorded during seizure initiation in some patients with epilepsy. Thus, beta-estradiol-induced NPY-sensitive filtering of 3 -5 Hz frequencies may be an important regulator of incoming seizure activity, but it could also serve a physiological purpose in modulating information flow into the hippocampus proper.