Microinjection of Reelin into the mPFC prevents MK-801-induced recognition memory impairment in mice
Microinjection of Reelin into the mPFC prevents MK-801-induced recognition memory impairment in mice
复制标题
将 Reelin 显微注射到 mPFC 中可预防 MK-801 诱导的小鼠识别记忆障碍
DOI：
10.1016/j.phrs.2021.105832
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发表时间：
2021
影响因子：
9.3
通讯作者：
Yamada Kiyofumi
中科院分区：
文献类型：
--
作者：
Sawahata Masahito;Asano Hiroki;Nagai Taku;Ito Norimichi;Kohno Takao;Nabeshima Toshitaka;Hattori Mitsuharu;Yamada Kiyofumi
Reelin是一种大的细胞外基质蛋白，有助于调节神经元的可塑性和认知功能。几项研究表明，由诸如基因SNDN突变或低Reelin表达等因素引起的Reelin功能障碍与精神分裂症（SCZ）相关。我们以前报道，微量注射Reelin到脑室防止苯环己哌啶诱导的认知和感觉运动门控缺陷。然而，目前尚不清楚Reelin是否以及如何改善SCZ动物模型中的行为异常。在本研究中，我们评估了重组Reelin注射到内侧前额叶皮层（mPFC）对MK-801（一种N-甲基-D-天冬氨酸受体拮抗剂）诱导的异常行为的影响。在新物体识别试验（NORT）中，向mPFC中微量注射Reelin可预防MK-801处理小鼠的识别记忆受损。另一方面，相同的处理对前脉冲抑制和Y-迷宫测试中的感觉-运动门控和短期记忆缺陷没有影响。为了建立对Reelin应答的神经基质，测定mPFC中c-Fos阳性细胞的数量。与生理盐水处理小鼠相比，MK-801处理小鼠mPFC中的c-Fos阳性细胞显著增加，并且向mPFC中微量注射Reelin可抑制该变化。不能与其受体结合的K2360/2467 A Reelin未能改善MK-801诱导的NORT认知缺陷。这些结果表明，Reelin通过作用于其受体抑制小鼠mPFC中的神经活动来预防MK-801诱导的识别记忆障碍。
Reelin, a large extracellular matrix protein, helps to regulate neuronal plasticity and cognitive function. Several studies have shown that Reelin dysfunction, resulting from factors such as mutations in gene RELN or low Reelin expression, is associated with schizophrenia (SCZ). We previously reported that microinjection of Reelin into cerebral ventricle prevents phencyclidine-induced cognitive and sensory-motor gating deficits. However, it remains unclear whether and how Reelin ameliorates behavioral abnormalities in the animal model of SCZ. In the present study, we evaluated the effect of recombinant Reelin microinjection into the medial prefrontal cortex (mPFC) on abnormal behaviors induced by MK-801, an N-methyl-D-aspartate receptor antagonist. Microinjection of Reelin into the mPFC prevented impairment of recognition memory of MK-801-treated mice in the novel object recognition test (NORT). On the other hand, the same treatment had no effect on deficits in sensory-motor gating and short-term memory in the pre-pulse inhibition and Y-maze tests, respectively. To establish the neural substrates that respond to Reelin, the number of c-Fos-positive cells in the mPFC was determined. A significant increase in c-Fos-positive cells in the mPFC of MK-801-treated mice was observed when compared with saline-treated mice, and this change was suppressed by microinjection of Reelin into the mPFC. A K2360/2467A Reelin that cannot bind to its receptor failed to ameliorate MK-801-induced cognitive deficits in NORT. These results suggest that Reelin prevents MK-801-induced recognition memory impairment by acting on its receptors to suppress neural activity in the mPFC of mice.