Smith Jeffrey P, Lal Varsha, Bowser David, Cappai Roberto, Masters Colin L, Ciccotosto Giuseppe D
Colorado State University-Pueblo, Pueblo, CO 81001, USA.
Brain Res. 2009 May 7;1269:176-84. doi: 10.1016/j.brainres.2009.03.007. Epub 2009 Mar 18.
Increasing evidence has pointed to inhibition of Long Term Potentiation (LTP) by soluble A beta 42 oligomers as central in the etiology of the learning and memory deficits that are hallmarks of Alzheimer Disease. These effects are thought to occur by an interaction between A beta 42 and certain cellular effectors that induce LTP, however, the precise identity of the A beta 42-interactive signaling molecules is unknown. Identification of such effectors is made more difficult because LTP induced by different stimulation protocols can be expressed through heterogeneous signaling pathways. The aim of this study was to compare differences in the A beta 42-dependent levels of inhibition of LTPs that were induced using high frequency stimulation (HFS), versus theta burst stimulation (TBS). Our results show that untreated control brain slices tetanized with either HFS or TBS gave similar levels of LTP and post tetanic stimulation (PTP), suggesting that the response induced by either protocol was comparable. However, A beta 42 peptide significantly blocked LTP and PTP induced by HFS, but not when TBS was used. NMDA receptor antagonists, D-AP5 and ifenprodil, both blocked LTPs that were induced by HFS or TBS. We propose that unknown signaling effectors, other than the NMDA receptor, which are differentially involved in the induction of LTP by TBS, as compared to HFS, may be responsible for this resistance of TBS-induced LTP to A beta 42 dependent inhibition.
越来越多的证据表明，可溶性Aβ42寡聚体对长时程增强（LTP）的抑制作用是阿尔茨海默病标志性的学习和记忆缺陷病因的核心。这些作用被认为是通过Aβ42与某些诱导LTP的细胞效应器之间的相互作用而发生的，然而，与Aβ42相互作用的信号分子的确切身份尚不清楚。由于不同刺激方案诱导的LTP可通过异质信号通路表达，因此鉴定此类效应器变得更加困难。本研究的目的是比较使用高频刺激（HFS）与theta爆发刺激（TBS）诱导的LTP中，Aβ42依赖性抑制水平的差异。我们的结果表明，用HFS或TBS进行强直刺激的未处理对照脑片产生的LTP和强直后刺激（PTP）水平相似，这表明两种方案诱导的反应具有可比性。然而，Aβ42肽显著阻断了HFS诱导的LTP和PTP，但使用TBS时则没有。NMDA受体拮抗剂D-AP5和艾芬地尔均阻断了HFS或TBS诱导的LTP。我们提出，与HFS相比，TBS诱导LTP过程中差异参与的、除NMDA受体之外的未知信号效应器，可能是TBS诱导的LTP对Aβ42依赖性抑制具有抗性的原因。
