Velísková Jana, Velísek Libor
Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy, Albert Einstein College of Medicine and the Einstein/Montefiore Comprehensive Epilepsy Management Center, Bronx, New York 10461, USA.
J Neurosci. 2007 May 30;27(22):6054-63. doi: 10.1523/JNEUROSCI.0366-07.2007.
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 approximately 3-5 Hz) was NPY sensitive and involved Y1 receptors, whereas it was insensitive to GABA(B) 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.
齿状回将传入的活动过滤到海马体本部。它在学习和记忆以及癫痫等病理状态中发挥作用。齿状回的一些门区中间神经元表达神经肽Y（NPY），其可调节颗粒细胞的活动。表达NPY的抑制性中间神经元亚群对癫痫发作诱导的损伤敏感。在去卵巢大鼠中用β-雌二醇预处理可保护门区中间神经元免受癫痫发作诱导的损伤，包括含NPY的损伤敏感亚群。在此，我们证明β-雌二醇可增强门区中间神经元内NPY的表达。在体外对混合穿通通路进行配对脉冲刺激发现，β-雌二醇可诱导颗粒细胞网络抑制增强，在200至300毫秒的刺激间隔（对应于约3 - 5赫兹）时，这种增强对NPY敏感且涉及Y1受体，而对GABA(B)或代谢型谷氨酸受体拮抗剂不敏感。此外，β-雌二醇预处理可减弱低频（3.3或5赫兹）爆发活动通过齿状回的传播。与单独用β-雌二醇处理的大鼠相比，通过脑室内注射抗NPY抗体清除内源性NPY可加速海人酸诱导的癫痫发作起始，并增加门区癫痫发作诱导的神经元损伤。总之，我们表明β-雌二醇上调门区NPY，这导致齿状回对3至5赫兹传入频率的抑制增强。这样的频率类似于一些癫痫患者癫痫发作起始时记录到的放电频率。因此，β-雌二醇诱导的对3 - 5赫兹频率的NPY敏感过滤可能是传入癫痫活动的重要调节因子，但它也可能在调节进入海马体本部的信息流中发挥生理作用。
