Abstract
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.
Highlights
IRRITABLE BOWEL SYNDROME (IBS) is a common, functional gastrointestinal disorder disease with the symptoms of repeated visceral pain and altered bowel habit (Canavan et al 2014)
These results suggest that neonatal neonatal maternal separation (NMS) significantly increased the visceromotor response to colorectal distension (CRD) in adult rats when compared with that in controls
high-frequency stimulation (HFS)-induced Long-term potentiation (LTP) at Schaffer collateral (SC)-Cornu Ammonis area 1 (CA1) synapses significantly increased in the rats of IBS (Chen et al 2014)
Summary
IRRITABLE BOWEL SYNDROME (IBS) is a common, functional gastrointestinal disorder disease with the symptoms of repeated visceral pain and altered bowel habit (Canavan et al 2014). Long-term potentiation (LTP), as a model of synaptic plasticity changes, is believed to be the key to neuronal functions for learning and memory (Bliss and Collingridge 1993; Chen et al 2012; Gerlai 2002). Whether hippocampal LTP is related to chronic visceral pain is still unknown. Whether hippocampal PKM contributes to the maintenance of LTP in rats of NMS remains unsolved so far. The effects of -pseudosubstrate inhibitory peptide (ZIP), a selective PKM inhibitor, on the inducement and maintenance of hippocampal LTP were tested by electrophysiological recordings in vitro. PKM ENHANCES HIPPOCAMPAL LTP IN CHRONIC VISCERAL PAIN injections of ZIP on visceral hypersensitivity were evaluated with EMG measurements in vivo. The open-field test and water-maze experiments were used to examine whether ZIP had side effects on movement and learning memory
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