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【Brain】可溶性Aβ独立于血管因素之外影响认知功
Soluble amyloid-β peptides potently disrupt hippocampal synaptic plasticity in the absence of cerebrovascular dysfunction in vivo
Neng-Wei Hu1,2, Imelda M. Smith3, Dominic M. Walsh3 and Michael J. Rowan1,2
1Trinity College Institute of Neuroscience, 2Department of Pharmacology and Therapeutics, Trinity College, Dublin 2 and 3Laboratory for Neurodegenerative Research, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
Correspondence to: Michael J. Rowan, Department of Pharmacology and Therapeutics, Biotechnology Building, Trinity College, Dublin 2, Ireland E-mail: mrowan@tcd.ie.
Long before the onset of clinical Alzheimer's disease non-fibrillar, soluble assembly states of amyloid-β (Aβ) peptides are believed to cause cognitive problems by disrupting synaptic function in the absence of significant neurodegeneration. Since many of the risk factors for Alzheimer's disease are vascular, impairment of cerebral blood flow by soluble Aβ has been proposed to be critical in triggering these early changes. However, it is not known if soluble Aβ can affect cerebrovascular function at the concentrations required to cause inhibition of synaptic plasticity mechanisms believed to underlie the early cognitive deficits of Alzheimer's disease. Here we developed a new method to simultaneously assess the ability of soluble Aβ to impair plasticity at synapses and to affect resting and activity-dependent local blood flow in the rat hippocampus in vivo. Intracerebroventricular injection of soluble synthetic Aβ40 dimers rapidly inhibited plasticity of excitatory synaptic transmission at doses (10–42 pmol) comparable to natural Aβ, but failed to affect vascular function measured using laser-Doppler flowmetry (LDF). Like wild-type Aβ40, the more vasculotropic Aβ produced by people with familial hemorrhagic stroke of the Dutch type (Aβ40E22Q), impaired hippocampal plasticity without causing a significant change in local blood flow. Furthermore, neither resting nor activation-evoked hippocampal perfusion was affected by soluble Aβ42, even at a concentration that markedly (25%) reduced baseline synaptic transmission. These findings demonstrate that the putative synaptotoxic soluble Aβ species of early Alzheimer's disease cause synaptic dysfunction in the absence of detectible changes in local blood flow. This strongly indicates that early cognitive deficits can be caused by soluble Aβ independently of deleterious effects on cerebrovascular dynamics. 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 Soluble amyloid-β peptides potently disrupt hippocampal synaptic plasticity in the absence of cerebrovascular dysfunction in vivo
在体内，可溶性Aβ独立于脑血管机能缺失之外影响海马区突触可塑性（认知功能）。
Long before the onset of clinical Alzheimer's disease non-fibrillar, soluble assembly states of amyloid-β (Aβ) peptides are believed to cause cognitive problems by disrupting synaptic function in the absence of significant neurodegeneration.
临床的阿尔茨海默病发病很早之前，非纤维可溶性聚集态Aβ就被认为独立于明显的神经变性之外影响突触功能，导致认知功能障碍。
Since many of the risk factors for Alzheimer's disease are vascular, impairment of cerebral blood flow by soluble Aβ has been proposed to be critical in triggering these early changes.
由于阿尔茨海默病的许多危险因子是血管性的，故提出可溶性Aβ 所致脑部血流减少在引起这些早期病变中起着关键性作用。
However, it is not known if soluble Aβ can affect cerebrovascular function at the concentrations required to cause inhibition of synaptic plasticity mechanisms believed to underlie the early cognitive deficits of Alzheimer's disease.
处于必需的浓集物状态的可溶性Aβ 能够影响脑血管功能，导致突触可塑性的抑制，然而，并不清楚这种机制是否是阿尔茨海默病早期认知缺陷的基础。
Here we developed a new method to simultaneously assess the ability of soluble Aβ to impair plasticity at synapses and to affect resting and activity-dependent local blood flow in the rat hippocampus in vivo
我们发展了新方法，即在大鼠活体的海马区进行试验以同时评价可溶性Aβ损伤突触可塑性以及影响静止的功能依赖性的局部血流的能力。
Intracerebroventricular injection of soluble synthetic Aβ40 dimers rapidly inhibited plasticity of excitatory synaptic transmission at doses (10–42 pmol) comparable to natural Aβ, but failed to affect vascular function measured using laser-Doppler flowmetry (LDF).
脑室内注射合成的可溶性Aβ40二聚体（10-42 pmol）即可迅速抑制兴奋性突触传递，这与天然的Aβ是相似的，但是通过LDF监测发现对血管功能并没有影响。
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作者:admin@医学,生命科学 2011-05-27 17:14
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