Involvement of protein kinase ζ in the maintenance of hippocampal long-term potentiation in rats with chronic visceral hypersensitivity.
Involvement of protein kinase ζ in the maintenance of hippocampal long-term potentiation in rats with chronic visceral hypersensitivity.
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DOI：
10.1152/jn.00929.2014
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发表时间：
2015-05-01
影响因子：
2.5
通讯作者：
Lin C
中科院分区：
文献类型：
--
作者：
Chen A;Bao C;Tang Y;Luo X;Guo L;Liu B;Lin C
我们前期的研究发现，海马长时程增强（LTP）参与肠易激综合征大鼠内脏高敏感性的形成。最近的研究表明，蛋白激酶M β（PKM β）可能负责维持记忆形成中的LTP。然而，PKM β是否参与内脏高敏感性尚不清楚。本研究通过新生儿母亲分离（NMS）建立内脏高敏感性大鼠模型。通过记录腹外斜肌对结直肠扩张的反应来评估内脏高敏感性。结果表明，NMS大鼠海马LTP和内脏高敏感性明显增强。β-假底物抑制肽（ZIP）可剂量依赖性地抑制NMS大鼠氨角1区LTP的维持。Western blot结果显示，NMS大鼠海马磷酸化PKM β（p-PKM β）表达明显增加。此外，双侧海马内注射ZIP可剂量依赖性地减轻NMS大鼠的内脏高敏感性。在30 min时抑制作用最大，抑制作用持续1.5 ~ 2 h。此外，旷场实验和Morris水迷宫实验结果表明，ZIP对NMS大鼠的运动和空间程序记忆无明显影响。结论：p-PKM β可能是维持海马LTP的关键蛋白，可能是内脏高敏感的重要机制之一。
The hippocampal long-term potentiation (LTP) was implicated in the formation of visceral hypersensitivity in rats with irritable bowel syndrome in our previous study. Recent studies have shown that protein kinase M ζ (PKMζ) may be responsible for the maintenance of LTP in memory formation. However, it remains unclear whether PKMζ is involved in the visceral hypersensitivity. In this study, a rat model of visceral hypersensitivity was generated by neonatal maternal separation (NMS). The visceral hypersensitivity was assessed by recording responses of the external oblique abdominal muscle to colorectal distension. Our results demonstrated that hippocampal LTP and visceral hypersensitivity were enhanced significantly in rats of NMS. ζ-Pseudosubstrate inhibitory peptide (ZIP) could dose dependently inhibit the maintenance of Cornu Ammonis area 1 LTP in rats of NMS. Furthermore, Western blot data showed that the expression of hippocampal phosphorylated PKMζ (p-PKMζ) significantly increased in rats of NMS. In addition, bilateral intrahippocampal injections of ZIP attenuated the visceral hypersensitivity dose dependently in rats of NMS. The maximal inhibition was observed at 30 min, and significant inhibition lasted for 1.5–2 h after ZIP application. Besides, data from the open-field test and Morris water maze showed that ZIP did not influence the movement and spatial procedural memory in rats of NMS. In conclusion, p-PKMζ might be a critical protein in the maintenance of hippocampal LTP, which could result in visceral hypersensitivity.
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