Time-Dependent Reversal of Long-Term Potentiation by an Integrin Antagonist
Time-Dependent Reversal of Long-Term Potentiation by an Integrin Antagonist
复制标题
整合素拮抗剂对长时程增强作用的时间依赖性逆转
作者：
U. Stäubli;Daniel Chun;G. Lynch
将整合素拮抗剂Gly-Arg-Gly-Asp-Ser-Pro(Gly-Arg-Gly-Asp-Ser-Pro，GRGDSP)局部注射于海马脑片两个记录点之一，分别于刺激Theta Burst诱发长时程增强(LTP)前后不同时间给予GRGDSP。诱导前10min、诱导后即刻和诱导后10min的应用使实验部位的LTP相对于切片内对照部位的LTP稳定地衰减。然而，在诱导后25min或更长时间给药对增强作用没有明显影响。当整合素拮抗剂被灌流到切片中而不是局部应用时，也得到了类似的结果。诱导后GRGDSP干扰LTP巩固的时间段相当于LTP易被低频传入刺激逆转和新形成的记忆易受各种干扰处理的时间段。使用阻断神经细胞黏附分子(NCAM)细胞外结合部位的多肽进行的可比实验没有产生LTP的时间依赖性逆转；即，与第四个免疫球蛋白样结构域相互作用的拮抗剂在诱导前而不是在诱导后应用时降低了LTP。此外，在抗NCAM纤维连接蛋白重复结构域的抗体存在下，LTP的形成正常发生。这些结果表明，在LTP诱导后的几分钟内，整合素的激活和信号传递是稳定突触增强所必需的，由此推断，可能需要将新的记忆转换为不容易被破坏的状态。
The integrin antagonist Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) was applied by local ejection to one of two recording sites in hippocampal slices at various times before and after long-term potentiation (LTP) was induced at both sites with theta burst stimulation. Applications 10 min before, immediately after, and 10 min after induction caused LTP at the experimental site to decay steadily relative to that at the within-slice control site. However, application at 25 min or more after induction had no detectable effect on potentiation. Similar results were obtained when the integrin antagonist was perfused into the slice rather than applied locally. The time period after induction during which GRGDSP interfered with LTP consolidation corresponds to that during which LTP is susceptible to reversal by low-frequency afferent stimulation and newly formed memories are vulnerable to various disruptive treatments. Comparable experiments using a peptide that blocks an extracellular binding site of neural cell adhesion molecules (NCAMs) did not yield time-dependent reversal of LTP; i.e., an antagonist that interacts with the fourth immunoglobulin-like domain reduced LTP when applied before induction but not afterward. Moreover, LTP formation occurred normally in the presence of an antibody against the fibronectin repeat domain of NCAM. These results suggest that integrin activation and signaling occurring over several minutes after LTP induction are necessary for stabilizing synaptic potentiation and by inference may be required for the conversion of new memories into a not readily disrupted state.
α3β1 整合素在细胞外基质组装中的新作用。
影响因子：
4
作者：
Wu,C;Chung,AE;McDonald,JA
通讯作者：
McDonald,JA
通过血小板糖蛋白 IIb/IIIa 受体的 RGD 类似物拮抗剂在体外解聚人血小板。
影响因子：
7.5
作者：
Haskel,EJ;Abendschein,DR
通讯作者：
Abendschein,DR