Prohormone convertase 2 (PC2) is essential for the biosynthesis of many neuropeptides, including several of them in hippocampus. In mouse brain, lacking an enzymatically active PC2 (PC2‐null) causes accumulation of many neuropeptides in their precursor or intermediate forms. Little is known about how a PC2‐null state may affect the function of the hippocampus. In this study, adult PC2‐null mice and their wildtype (WT) littermates were subjected to three analyses to determine possible changes associated with PC2‐null at physiological, behavioral, and molecular levels, respectively, under normal and stressed conditions. Electrophysiological recordings of hippocampal slices were performed to measure evoked field‐excitatory postsynaptic potentials (EPSP), long‐term potentiation (LTP), and paired‐pulse facilitation (PPF). Morris water maze (MWM) testing was conducted to examine behavioral changes that are indicative of hippocampal integrity. Quantitative mass spectrometry analysis was used to determine changes in the hippocampal proteome in response to a focal cerebral ischemic insult. We found that there were no significant differences in the threshold of evoked EPSPs between PC2‐null and WT animals. However, an increase in LTP in both triggering rate and amplitude was observed in PC2‐null mice, suggesting that PC2 may be involved in regulating synaptic strength. The PPF, on the other hand, showed a decrease in PC2‐null mice, suggesting a presynaptic mechanism. Consistent with changes in LTP, PC2‐null mice displayed decreased latencies in finding the escape platform in the MWM test. Further, after distal focal cerebral ischemia, the hippocampal proteomes incurred changes in both WT and PC2‐null mice, with a prominent change in proteins associated with neurotransmission, exocytosis, and transport processes seen in the PC2‐null but not WT mice. Taken together, our results suggest that PC2 is involved in regulating hippocampal synaptic plasticity, learning, and memory behaviors, as well as the hippocampal response to stresses originating in other regions of the brain.

中文翻译：

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缺乏活性激素原转化酶 2 的小鼠的海马变化。

激素原转化酶 2 (PC2) 对许多神经肽的生物合成至关重要，其中包括海马中的几种。在小鼠大脑中，缺乏酶活性 PC2（PC2-null）会导致许多神经肽以其前体或中间体形式积累。关于 PC2-null 状态如何影响海马体的功能知之甚少。在这项研究中，成年 PC2-null 小鼠及其野生型 (WT) 同窝小鼠接受了三种分析，以确定在正常和压力条件下分别在生理、行为和分子水平上与 PC2-null 相关的可能变化。进行海马切片的电生理记录以测量诱发场兴奋性突触后电位 (EPSP)、长时程增强 (LTP) 和成对脉冲易化 (PPF)。进行莫里斯水迷宫 (MWM) 测试以检查表明海马完整性的行为变化。定量质谱分析用于确定响应于局灶性脑缺血损伤的海马蛋白质组的变化。我们发现 PC2-null 和 WT 动物之间诱发 EPSP 的阈值没有显着差异。然而，在 PC2-null 小鼠中观察到 LTP 的触发率和振幅增加，表明 PC2 可能参与调节突触强度。另一方面，PPF 显示 PC2 缺失小鼠的减少，表明存在突触前机制。与 LTP 的变化一致，PC2-null 小鼠在 MWM 测试中寻找逃逸平台的延迟降低。此外，在远端局灶性脑缺血后，海马蛋白质组在 WT 和 PC2-null 小鼠中都发生了变化，与神经传递、胞吐作用和转运过程相关的蛋白质发生了显着变化，在 PC2-null 而非 WT 小鼠中观察到。总之，我们的结果表明 PC2 参与调节海马突触可塑性、学习和记忆行为，以及海马对源自大脑其他区域的压力的反应。