英國布里斯托大學(xué)的一項(xiàng)最新研究稱，該校研究人員發(fā)現(xiàn)了人類大腦中某些神經(jīng)細(xì)胞中風(fēng)期間的自我保護(hù)機(jī)制,，通過這一機(jī)制,，這些神經(jīng)細(xì)胞可以免受中風(fēng)的損害。研究人員稱,，這一發(fā)現(xiàn)有助于科學(xué)家找到新方法來保護(hù)其他類型神經(jīng)細(xì)胞免受中風(fēng)損害,，從而降低中風(fēng)對病人身體的影響。該研究成果發(fā)表在最新一期的《神經(jīng)科學(xué)期刊》上,。
中風(fēng)是一種急性腦血管病,，發(fā)病時(shí)患者大腦血液供應(yīng)中斷，使得腦神經(jīng)細(xì)胞無法獲得氧氣和養(yǎng)分而死亡,，致使大腦認(rèn)知功能的喪失,，造成失語、癱瘓等癥狀,。該病致殘率和致死率都很高，且容易復(fù)發(fā),，是威脅人類健康的重要?dú)⑹?。在英國中風(fēng)是第三大致死疾病。
有研究表明,，在中風(fēng)時(shí),，并不是所有的腦神經(jīng)細(xì)胞都會(huì)受到損害，而找到這些神經(jīng)細(xì)胞免受損害的原因,，就可以找出辦法來保護(hù)其他的神經(jīng)細(xì)胞,。為找到部分腦神經(jīng)細(xì)胞免受中風(fēng)損害的機(jī)制，英國布里斯托大學(xué)的研究人員對人類大腦海馬體中的兩種類型神經(jīng)細(xì)胞——CA1細(xì)胞和CA3細(xì)胞進(jìn)行了研究分析,。這兩種類型細(xì)胞中,，CA1細(xì)胞極易受到中風(fēng)損害，而CA3細(xì)胞雖與CA1細(xì)胞有許多相似之處,，卻有一定的抗性,，不易受到中風(fēng)損害。
研究人員發(fā)現(xiàn),，在中風(fēng)時(shí),，大腦會(huì)釋放大量的神經(jīng)遞質(zhì)谷氨酸，CA3細(xì)胞能夠通過移除其表面的谷氨酸受體蛋白來減少對神經(jīng)遞質(zhì)谷氨酸的敏感性,。進(jìn)一步研究發(fā)現(xiàn),，CA3細(xì)胞移除谷氨酸受體的機(jī)制是由腺苷酸A3受體所引發(fā)，這種受體只有在中風(fēng)后神經(jīng)遞質(zhì)腺苷酸達(dá)到了非常高的水平時(shí)才會(huì)被激活,。而CA1細(xì)胞不擁有腺苷酸A3受體,，無法移除細(xì)胞表面的谷氨酸受體,，因而對中風(fēng)損害十分敏感。
該項(xiàng)研究領(lǐng)導(dǎo)者,、布里斯托大學(xué)的杰克·梅洛博士表示,，中風(fēng)的治療之所以非常困難，是因?yàn)槠浒l(fā)病很難預(yù)測,，且需要在發(fā)病后幾分鐘內(nèi)及時(shí)進(jìn)行藥物治療,。雖然他們的研究發(fā)現(xiàn)并不能完全解決這一問題，但其所揭露的CA3細(xì)胞自我保護(hù)機(jī)制,，有助于科學(xué)家找到新方法來保護(hù)其他類型的神經(jīng)細(xì)胞,，從而降低中風(fēng)對人類健康造成的損害。(生物谷 Bioon.com)
doi:10.1523/?JNEUROSCI.1183-11.2011
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Oxygen/Glucose Deprivation Induces a Reduction in Synaptic AMPA Receptors on Hippocampal CA3 Neurons Mediated by mGluR1 and Adenosine A3 Receptors
Siobhan H. Dennis1, Nadia Jaafari2, Helena Cimarosti2,3, Jonathan G. Hanley2, Jeremy M. Henley2, and Jack R. Mellor1
Hippocampal CA1 pyramidal neurons are highly sensitive to ischemic damage, whereas neighboring CA3 pyramidal neurons are less susceptible. It is proposed that switching of AMPA receptor (AMPAR) subunits on CA1 neurons during an in vitro model of ischemia, oxygen/glucose deprivation (OGD), leads to an enhanced permeability of AMPARs to Ca2+, resulting in delayed cell death. However, it is unclear whether the same mechanisms exist in CA3 neurons and whether this underlies the differential sensitivity to ischemia. Here, we investigated the consequences of OGD for AMPAR function in CA3 neurons using electrophysiological recordings in rat hippocampal slices. Following a 15 min OGD protocol, a substantial depression of AMPAR-mediated synaptic transmission was observed at CA3 associational/commissural and mossy fiber synapses but not CA1 Schaffer collateral synapses. The depression of synaptic transmission following OGD was prevented by metabotropic glutamate receptor 1 (mGluR1) or A3 receptor antagonists, indicating a role for both glutamate and adenosine release. Inhibition of PLC, PKC, or chelation of intracellular Ca2+ also prevented the depression of synaptic transmission. Inclusion of peptides to interrupt the interaction between GluA2 and PICK1 or dynamin and amphiphysin prevented the depression of transmission, suggesting a dynamin and PICK1-dependent internalization of AMPARs after OGD. We also show that a reduction in surface and total AMPAR protein levels after OGD was prevented by mGluR1 or A3 receptor antagonists, indicating that AMPARs are degraded following internalization. Thus, we describe a novel mechanism for the removal of AMPARs in CA3 pyramidal neurons following OGD that has the potential to reduce excitotoxicity and promote neuroprotection.
