Inserm, Mixed Research Unit in Health U919, University Caen Basse Normandie, Serine Proteases and Pathophysiology of the Neurovascular Unit, Public Interest Group CYCERON, F-14074 Caen, France.
J Neurosci. 2012 Sep 12;32(37):12726-34. doi: 10.1523/JNEUROSCI.6202-11.2012.
Tissue plasminogen activator (tPA) is a serine protease with pleiotropic actions in the CNS, such as synaptic plasticity and neuronal death. Some effects of tPA require its interaction with the GluN1 subunit of the NMDA receptor (NMDAR), leading to a potentiation of NMDAR signaling. We have reported previously that the pro-neurotoxic effect of tPA is mediated through GluN2D subunit-containing NMDARs. Thus, the aim of the present study was to determine whether GluN2D subunit-containing NMDARs drive tPA-mediated cognitive functions. To address this issue, a strategy of immunization designed to prevent the in vivo interaction of tPA with NMDARs and GluN2D-deficient mice were used in a set of behavioral tasks. Altogether, our data provide the first evidence that tPA influences spatial memory through its preferential interaction with GluN2D subunit-containing NMDARs.
组织型纤溶酶原激活物（tPA）是一种丝氨酸蛋白酶，在中枢神经系统中具有多种作用，如突触可塑性和神经元死亡。tPA 的一些作用需要其与 NMDA 受体（NMDAR）的 GluN1 亚基相互作用，从而增强 NMDAR 信号。我们之前曾报道过，tPA 的促神经毒性作用是通过包含 GluN2D 亚基的 NMDAR 介导的。因此，本研究的目的是确定是否包含 GluN2D 亚基的 NMDAR 驱动 tPA 介导的认知功能。为了解决这个问题，我们使用了一种旨在防止 tPA 与 NMDAR 和 GluN2D 缺失型小鼠体内相互作用的免疫接种策略，在一系列行为任务中进行了研究。总之，我们的数据提供了第一个证据，表明 tPA 通过与其优先相互作用的包含 GluN2D 亚基的 NMDAR 影响空间记忆。
