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Ketamine inhibits proliferation of neural stem cell from neonatal rat hippocampus in vitro.
Cell Physiol Biochem. 2014; 34(5):1792-801.CP

Abstract

BACKGROUND/AIMS

Ketamine is a widely used anesthetic in obstetric and pediatric anesthesia. In the developing brain, the widespread neuron apoptosis triggered by ketamine has been demonstrated. However, little is known about its effect on neural stem cells (NSCs) function. This study aimed to investigate the effect of ketamine on proliferation of NSCs from neonatal rat hippocampus.

METHODS

Neural stem cells were isolated from the hippocampus of Sprague-Dawley rats on postnatal day 3. In dose-response experiments, cultured neural stem cells (NSCs) were exposed to different concentrations of ketamine (0-1000 µM) for 24 hrs. The proliferative activity of NSCs was evaluated by 5-Bromo-2'-deoxyuridine (BrdU) incorporation assay. Apoptosis of neural stem cells were assessed using caspase-3 by western blot. The intracellular Ca(2+) concentration ([Ca(2+)]i) in NSCs was analyzed by flow cytometry. The activation of protein kinase C-α (PKCα) and the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) were measured by western blot analysis.

RESULTS

Clinical relevant concentration of ketamine (10, 20 and 50 µM) did not markedly alter the proliferation of NSCs from neonatal rat hippocampus in vitro. However, ketamine (200, 500, 800 and 1000μM) significantly inhibited the proliferation of NSCs and did not affect the expression of caspase-3. Meanwhile, ketamine (200, 500, 800 and 1000μM) also markedly decreased [Ca(2+)]i as well as suppressed PKCα activation and ERK1/2 phosphorylation in NSCs. A combination of subthreshold concentrations of ketamine (100 μM) and Ca(2+) channel blocker verapamil (2.5 μM), PKCα inhibitor chelerythrine (2.5 μM) or ERK1/2 kinase inhibitor PD98059 (5 μM) significantly produced suprathreshold effects on PKCα activation, ERK1/2 phosphorylation and NSC proliferation.

CONCLUSION

Ketamine inhibited proliferation of NSCs from neonatal rat hippocampus in vitro. Suppressing Ca(2+)-PKCα-ERK1/2 signaling pathway may be involved in this inhibitory effect of ketamine on NSCs proliferation.

Authors+Show Affiliations

Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, P R. China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25427956

Citation

Wu, Yu-Qing, et al. "Ketamine Inhibits Proliferation of Neural Stem Cell From Neonatal Rat Hippocampus in Vitro." Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 34, no. 5, 2014, pp. 1792-801.
Wu YQ, Liang T, Huang H, et al. Ketamine inhibits proliferation of neural stem cell from neonatal rat hippocampus in vitro. Cell Physiol Biochem. 2014;34(5):1792-801.
Wu, Y. Q., Liang, T., Huang, H., Zhu, Y. Z., Zhao, P. P., Xu, C. M., Liu, L., Shi, X. T., Hu, Y., Huang, L., & Zhou, C. H. (2014). Ketamine inhibits proliferation of neural stem cell from neonatal rat hippocampus in vitro. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 34(5), 1792-801. https://doi.org/10.1159/000366379
Wu YQ, et al. Ketamine Inhibits Proliferation of Neural Stem Cell From Neonatal Rat Hippocampus in Vitro. Cell Physiol Biochem. 2014;34(5):1792-801. PubMed PMID: 25427956.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ketamine inhibits proliferation of neural stem cell from neonatal rat hippocampus in vitro. AU - Wu,Yu-Qing, AU - Liang,Tuo, AU - Huang,He, AU - Zhu,Yang-Zi, AU - Zhao,Pan-Pan, AU - Xu,Chun-Mei, AU - Liu,Lu, AU - Shi,Xiao-Tian, AU - Hu,Yu, AU - Huang,Li, AU - Zhou,Cheng-Hua, Y1 - 2014/11/14/ PY - 2014/09/09/accepted PY - 2014/11/28/entrez PY - 2014/11/28/pubmed PY - 2015/8/15/medline SP - 1792 EP - 801 JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JO - Cell. Physiol. Biochem. VL - 34 IS - 5 N2 - BACKGROUND/AIMS: Ketamine is a widely used anesthetic in obstetric and pediatric anesthesia. In the developing brain, the widespread neuron apoptosis triggered by ketamine has been demonstrated. However, little is known about its effect on neural stem cells (NSCs) function. This study aimed to investigate the effect of ketamine on proliferation of NSCs from neonatal rat hippocampus. METHODS: Neural stem cells were isolated from the hippocampus of Sprague-Dawley rats on postnatal day 3. In dose-response experiments, cultured neural stem cells (NSCs) were exposed to different concentrations of ketamine (0-1000 µM) for 24 hrs. The proliferative activity of NSCs was evaluated by 5-Bromo-2'-deoxyuridine (BrdU) incorporation assay. Apoptosis of neural stem cells were assessed using caspase-3 by western blot. The intracellular Ca(2+) concentration ([Ca(2+)]i) in NSCs was analyzed by flow cytometry. The activation of protein kinase C-α (PKCα) and the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) were measured by western blot analysis. RESULTS: Clinical relevant concentration of ketamine (10, 20 and 50 µM) did not markedly alter the proliferation of NSCs from neonatal rat hippocampus in vitro. However, ketamine (200, 500, 800 and 1000μM) significantly inhibited the proliferation of NSCs and did not affect the expression of caspase-3. Meanwhile, ketamine (200, 500, 800 and 1000μM) also markedly decreased [Ca(2+)]i as well as suppressed PKCα activation and ERK1/2 phosphorylation in NSCs. A combination of subthreshold concentrations of ketamine (100 μM) and Ca(2+) channel blocker verapamil (2.5 μM), PKCα inhibitor chelerythrine (2.5 μM) or ERK1/2 kinase inhibitor PD98059 (5 μM) significantly produced suprathreshold effects on PKCα activation, ERK1/2 phosphorylation and NSC proliferation. CONCLUSION: Ketamine inhibited proliferation of NSCs from neonatal rat hippocampus in vitro. Suppressing Ca(2+)-PKCα-ERK1/2 signaling pathway may be involved in this inhibitory effect of ketamine on NSCs proliferation. SN - 1421-9778 UR - https://www.unboundmedicine.com/medline/citation/25427956/Ketamine_inhibits_proliferation_of_neural_stem_cell_from_neonatal_rat_hippocampus_in_vitro_ L2 - https://www.karger.com?DOI=10.1159/000366379 DB - PRIME DP - Unbound Medicine ER -