title: Involvement of protein kinase ζ in the maintenance of hippocampal long-term potentiation in rats with chronic visceral hypersensitivity.
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.
authors.affiliation: Fujian Medical University, School of Basic Medical Sciences, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fuzhou City, Fujian Province, People's Republic of China.
authors.forename: Aiqin
authors.initials: A
authors.lastname: Chen
authors.affiliation: Fujian Medical University, School of Basic Medical Sciences, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fuzhou City, Fujian Province, People's Republic of China.
authors.forename: Chengjia
authors.initials: C
authors.lastname: Bao
authors.affiliation: Fujian Medical University, School of Basic Medical Sciences, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fuzhou City, Fujian Province, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Fujian Medical University, School of Basic Medical Sciences, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fuzhou City, Fujian Province, People's Republic of China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Luo
authors.affiliation: Fujian Medical University, School of Basic Medical Sciences, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fuzhou City, Fujian Province, People's Republic of China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Guo
authors.affiliation: Fujian Medical University, School of Basic Medical Sciences, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fuzhou City, Fujian Province, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Fujian Medical University, School of Basic Medical Sciences, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fuzhou City, Fujian Province, People's Republic of China chunlin77550@126.com.
authors.forename: Chun
authors.initials: C
authors.lastname: Lin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D057846:Cell-Penetrating Peptides; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004576:Electromyography; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D066298:In Vitro Techniques; D055666:Lipopeptides / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008426:Maternal Deprivation; D018782:Maze Learning / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D059265:Visceral Pain / Q000378:metabolism / Q000473:pathology*; D000099221:Protein Kinase C zeta
chemical_list: D057846:Cell-Penetrating Peptides; D055666:Lipopeptides; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta; C568285:zeta-inhibitory peptide
keywords: chronic visceral pain; hippocampus; long-term potentiation; neonatal maternal separation; protein kinase M ζ