Brain-enriched guanylate kinase-associated protein (BEGAIN) is highly enriched in the post-synaptic density (PSD) fraction and was identified in our previous study as a protein associated with neuropathic pain in the spinal dorsal horn. PSD protein complexes containing N-methyl-d-aspartate receptors are known to be involved in neuropathic pain. Since these PSD proteins also participate in learning and memory, BEGAIN is also expected to play a crucial role in this behavior. To verify this, we first examined the distribution of BEGAIN in the brain. We found that BEGAIN was widely distributed in the brain and highly expressed in the dendritic regions of the hippocampus. Moreover, we found that BEGAIN was concentrated in the PSD fraction of the hippocampus. Furthermore, immunoelectron microscopy confirmed that BEGAIN was localized at the asymmetric synapses. Behavioral tests were performed using BEGAIN-knockout (KO) mice to determine the contribution of BEGAIN toward learning and memory. Spatial reference memory and reversal learning in the Barns circular maze test along with contextual fear and cued fear memory in the contextual and cued fear conditioning test were significantly impaired in BEGAIN-KO mice compared to with those in wild-type mice. Thus, this study reveals that BEGAIN is a component of the post-synaptic compartment of excitatory synapses involved in learning and memory.

脑富集鸟苷酸激酶相关蛋白 (BEGAIN) 在突触后密度 (PSD) 部分高度富集，在我们之前的研究中被鉴定为与脊髓背角神经性疼痛相关的蛋白质。已知含有N-甲基-d-天冬氨酸受体的 PSD 蛋白复合物与神经性疼痛有关。由于这些 PSD 蛋白也参与学习和记忆，因此 BEGAIN 也有望在这种行为中发挥至关重要的作用。为了验证这一点，我们首先检查了 BEGAIN 在大脑中的分布。我们发现BEGAIN在大脑中广泛分布，并在海马树突区高表达。此外，我们发现 BEGAIN 集中在海马的 PSD 部分。此外，免疫电子显微镜证实 BEGAIN 位于不对称突触处。使用 BEGAIN 基因敲除 (KO) 小鼠进行行为测试，以确定 BEGAIN 对学习和记忆的贡献。与野生型小鼠相比，BEGAIN-KO 小鼠的 Barns 圆形迷宫测试中的空间参考记忆和逆转学习以及情境恐惧和暗示恐惧条件反射测试中的情境恐惧记忆均显着受损。因此，这项研究揭示了 BEGAIN 是参与学习和记忆的兴奋性突触突触后区室的一个组成部分。