英国布里斯托大学的一项最新研究称，该校研究人员发现了人类大脑中某些神经细胞中风期间的自我保护机制，通过这一机制，这些神经细胞可以免受中风的损害。研究人员称，这一发现有助于科学家找到新方法来保护其他类型神经细胞免受中风损害，从而降低中风对病人身体的影响。该研究成果发表在最新一期的《神经科学期刊》上。
中风是一种急性脑血管病，发病时患者大脑血液供应中断，使得脑神经细胞无法获得氧气和养分而死亡，致使大脑认知功能的丧失，造成失语、瘫痪等症状。该病致残率和致死率都很高，且容易复发，是威胁人类健康的重要杀手。在英国中风是第三大致死疾病。
有研究表明，在中风时，并不是所有的脑神经细胞都会受到损害，而找到这些神经细胞免受损害的原因，就可以找出办法来保护其他的神经细胞。为找到部分脑神经细胞免受中风损害的机制，英国布里斯托大学的研究人员对人类大脑海马体中的两种类型神经细胞——CA1细胞和CA3细胞进行了研究分析。这两种类型细胞中，CA1细胞极易受到中风损害，而CA3细胞虽与CA1细胞有许多相似之处，却有一定的抗性，不易受到中风损害。
研究人员发现，在中风时，大脑会释放大量的神经递质谷氨酸，CA3细胞能够通过移除其表面的谷氨酸受体蛋白来减少对神经递质谷氨酸的敏感性。进一步研究发现，CA3细胞移除谷氨酸受体的机制是由腺苷酸A3受体所引发，这种受体只有在中风后神经递质腺苷酸达到了非常高的水平时才会被激活。而CA1细胞不拥有腺苷酸A3受体，无法移除细胞表面的谷氨酸受体，因而对中风损害十分敏感。
该项研究领导者、布里斯托大学的杰克·梅洛博士表示，中风的治疗之所以非常困难，是因为其发病很难预测，且需要在发病后几分钟内及时进行药物治疗。虽然他们的研究发现并不能完全解决这一问题，但其所揭露的CA3细胞自我保护机制，有助于科学家找到新方法来保护其他类型的神经细胞，从而降低中风对人类健康造成的损害。(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.
