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首页> 外文期刊>The European Journal of Neuroscience >Soluble Arctic amyloid beta protein inhibits hippocampal long-term potentiation in vivo.
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Soluble Arctic amyloid beta protein inhibits hippocampal long-term potentiation in vivo.

机译：可溶性北极淀粉样β蛋白在体内抑制海马长时程增强。

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摘要

Abstract Mutations in the amyloid precursor protein that result in substitutions of glutamic acid at residue 22 of the amyloid beta protein (Abeta) with glutamine (Q22, Dutch) or glycine (G22, Arctic) cause aggressive familial neurological diseases characterized by cerebrovascular haemorrhages or Alzheimer's-type dementia, respectively. The present study compared the ability of these peptides to block long-term potentiation (LTP) of glutamatergic transmission in the hippocampus in vivo. The effects of intracerebroventricular injection of wild-type, Q22 and G22 Abeta(1-40) peptides were examined in the CA1 area of urethane-anaesthetized rats. Both mutant peptides were approximately 100-fold more potent than wild-type Abeta at inhibiting LTP induced by high-frequency stimulation when solutions of Abeta were freshly prepared. Fibrillar material, as determined by electron microscopy, was obvious in all these peptide solutions and exhibited appreciable Congo Red binding, particularly for Abeta(1-40)G22 and Abeta(1-40)Q22. A soluble fraction of Abeta(1-40)G22, obtained following high-speed centrifugation, retained full activity of the peptide solution to inhibit LTP, providing strong evidence that in the case of the Arctic disease a soluble nonfibrillar form of Abeta may represent the primary mediator of Abeta-related cognitive deficits, particularly early in the disease. In contrast, nonfibrillar soluble Abeta(1-40)Q22 supernatant solution was approximately 10-fold less potent at inhibiting LTP than Abeta(1-40)G22, a finding consistent with fibrillar Abeta contributing to the inhibition of LTP by the Dutch peptide.
机译：摘要淀粉样蛋白前体蛋白的突变导致谷氨酰胺（Q22，荷兰人）或甘氨酸（G22，北极）中的淀粉样蛋白β蛋白（Abeta）第22位残基被谷氨酸取代，引起侵袭性家族性神经疾病，其特征是脑血管出血或阿尔茨海默氏病型痴呆。本研究比较了这些肽在体内阻断海马中谷氨酸能传递的长期增强（LTP）的能力。脑室注射野生型，Q22和G22 Abeta（1-40）肽的脑室内注射的尿烷麻醉大鼠的CA1区。当新鲜制备Abeta溶液时，两种突变体肽在抑制高频刺激诱导的LTP时，其效力比野生型Abeta高约100倍。通过电子显微镜确定的原纤维物质在所有这些肽溶液中均很明显，并且表现出可观的刚果红结合，特别是对于Abeta（1-40）G22和Abeta（1-40）Q22。高速离心后获得的Abeta（1-40）G22可溶性级分保留了肽溶液抑制LTP的全部活性，提供了强有力的证据表明在北极疾病的情况下，可溶性非原纤维形式的Abeta可能代表了Abeta相关认知缺陷的主要介质，尤其是在疾病早期。相反，非原纤维可溶性Abe​​ta（1-40）Q22上清液在抑制LTP上的效力比Abeta（1-40）G22低约10倍，这一发现与原纤维Abeta有助于荷兰肽抑制LTP一致。

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