Endogenous amyloid-β is necessary for hippocampal synaptic plasticity and memory.
Endogenous amyloid-β is necessary for hippocampal synaptic plasticity and memory.
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DOI：
10.1002/ana.22313
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发表时间：
2011-05
影响因子：
11.2
通讯作者：
Arancio, Ottavio
中科院分区：
文献类型：
--
作者：
Puzzo, Daniela;Privitera, Lucia;Fa, Mauro;Staniszewski, Agnieszka;Hashimoto, Gakuji;Aziz, Fahad;Sakurai, Mikako;Ribe, Elena M.;Troy, Carol M.;Mercken, Marc;Jung, Sonia S.;Palmeri, Agostino;Arancio, Ottavio
本研究旨在探讨内源性淀粉样β肽（Aβ）在正常脑组织中的作用。长时程增强（LTP），一种被认为与学习和记忆相关的突触可塑性，通过海马脑片CA1区的胞外场记录进行了研究，而行为技术被用来评估上下文恐惧记忆和参考记忆。通过小干扰RNA（siRNA）技术降低淀粉样前体蛋白（APP）的表达。我们发现抗啮齿类动物Aβ抗体和针对小鼠APP的siRNA都降低了LTP以及背景恐惧记忆和参考记忆。这些作用通过添加人Aβ42而得到挽救，表明内源性产生的Aβ是正常LTP和记忆所必需的。此外，内源性Aβ对可塑性和记忆的影响可能是由于调节递质释放、激活含α7的烟碱乙酰胆碱受体和Aβ42的产生。内源性Aβ42是正常中枢神经系统内突触可塑性和记忆的关键参与者。在设计旨在降低Aβ水平以治疗阿尔茨海默病的疗法时，需要考虑到这一点。
The goal of this study was to investigate the role of endogenous amyloid-β peptide (Aβ) in healthy brain. Long-term potentiation (LTP), a type of synaptic plasticity that is thought to be associated with learning and memory, was examined through extracellular field recordings from the CA1 region of hippocampal slices, whereas behavioral techniques were used to assess contextual fear memory and reference memory. Amyloid precursor protein (APP) expression was reduced through small interfering RNA (siRNA) technique. We found that both antirodent Aβ antibody and siRNA against murine APP reduced LTP as well as contextual fear memory and reference memory. These effects were rescued by the addition of human Aβ42, suggesting that endogenously produced Aβ is needed for normal LTP and memory. Furthermore, the effect of endogenous Aβ on plasticity and memory was likely due to regulation of transmitter release, activation of α7-containing nicotinic acetylcholine receptors, and Aβ42 production. Endogenous Aβ42 is a critical player in synaptic plasticity and memory within the normal central nervous system. This needs to be taken into consideration when designing therapies aiming at reducing Aβ levels to treat Alzheimer disease.
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影响因子：
11.4
作者：
Elbashir, SM;Martinez, J;Tuschl, T
通讯作者：
Tuschl, T
淀粉样蛋白β动力学与受伤的人脑中的神经系统状况相关。
影响因子：
56.9
作者：
Brody, David L.;Magnoni, Sandra;Schwetye, Kate E.;Spinner, Michael L.;Esparza, Thomas J.;Stocchetti, Nino;Zipfel, Gregory J.;Holtzman, David M.
通讯作者：
Holtzman, David M.
影响因子：
16.2
作者：
Kamenetz, F;Tomita, T;Malinow, R
通讯作者：
Malinow, R
影响因子：
5
作者：
Itoh, A;Akaike, T;Nabeshima, T
通讯作者：
Nabeshima, T
DOI：
10.1073/pnas.0602896103
发表时间：
2006-06-06
影响因子：
11.1
作者：
Malm, Tarja;Ortt, Michael;Koistinaho, Jari
通讯作者：
Koistinaho, Jari