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Ketamine Affects the Neurogenesis of the Hippocampal Dentate Gyrus in 7-Day-Old Rats.
Neurotox Res. 2016 08; 30(2):185-98.NR

Abstract

Ketamine has been reported to cause neonatal neurotoxicity via a neuronal apoptosis mechanism; however, no in vivo research has reported whether ketamine could affect postnatal neurogenesis in the hippocampal dentate gyrus (DG). A growing number of experiments suggest that postnatal hippocampal neurogenesis is the foundation of maintaining normal hippocampus function into adulthood. Therefore, this study investigated the effect of ketamine on hippocampal neurogenesis. Male Sprague-Dawley rats were divided into two groups: the control group (equal volume of normal saline), and the ketamine-anesthesia group (40 mg/kg ketamine in four injections at 1 h intervals). The S-phase marker 5-bromodeoxyuridine (BrdU) was administered after ketamine exposure to postnatal day 7 (PND-7) rats, and the neurogenesis in the hippocampal DG was assessed using single- or double-immunofluorescence staining. The expression of GFAP in the hippocampal DG was measured by western blot analysis. Spatial reference memory was tested by Morris water maze at 2 months after PND-7 rats exposed to ketamine treatment. The present results showed that neonatal ketamine exposure significantly inhibited neural stem cell (NSC) proliferation, decreased astrocytic differentiation, and markedly enhanced neuronal differentiation. The disruptive effect of ketamine on the proliferation and differentiation of NSCs lasted at least 1 week and disappeared by 2 weeks after ketamine exposure. Moreover, the migration of newborn neurons in the granule cell layer and the growth of astrocytes in the hippocampal DG were inhibited by ketamine on PND-37 and PND-44. Finally, ketamine caused a deficit in hippocampal-dependent spatial reference memory tasks at 2 months old. Our results suggested that ketamine may interfere with hippocampal neurogenesis and long-term neurocognitive function in PND-7 rats. These findings may provide a new perspective to explain the adult neurocognitive dysfunction induced by neonatal ketamine exposure.

Authors+Show Affiliations

Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China.Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China.Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China.Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China. xymzyqwu@126.com.

Pub Type(s)

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

Language

eng

PubMed ID

26966008

Citation

Huang, He, et al. "Ketamine Affects the Neurogenesis of the Hippocampal Dentate Gyrus in 7-Day-Old Rats." Neurotoxicity Research, vol. 30, no. 2, 2016, pp. 185-98.
Huang H, Liu CM, Sun J, et al. Ketamine Affects the Neurogenesis of the Hippocampal Dentate Gyrus in 7-Day-Old Rats. Neurotox Res. 2016;30(2):185-98.
Huang, H., Liu, C. M., Sun, J., Hao, T., Xu, C. M., Wang, D., & Wu, Y. Q. (2016). Ketamine Affects the Neurogenesis of the Hippocampal Dentate Gyrus in 7-Day-Old Rats. Neurotoxicity Research, 30(2), 185-98. https://doi.org/10.1007/s12640-016-9615-7
Huang H, et al. Ketamine Affects the Neurogenesis of the Hippocampal Dentate Gyrus in 7-Day-Old Rats. Neurotox Res. 2016;30(2):185-98. PubMed PMID: 26966008.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ketamine Affects the Neurogenesis of the Hippocampal Dentate Gyrus in 7-Day-Old Rats. AU - Huang,He, AU - Liu,Cun-Ming, AU - Sun,Jie, AU - Hao,Ting, AU - Xu,Chun-Mei, AU - Wang,Dan, AU - Wu,Yu-Qing, Y1 - 2016/03/10/ PY - 2015/12/15/received PY - 2016/03/01/accepted PY - 2016/02/22/revised PY - 2016/3/12/entrez PY - 2016/3/12/pubmed PY - 2017/7/18/medline KW - Hippocampal dentate gyrus KW - Ketamine KW - Morris water maze test KW - Neonatal KW - Neurogenesis SP - 185 EP - 98 JF - Neurotoxicity research JO - Neurotox Res VL - 30 IS - 2 N2 - Ketamine has been reported to cause neonatal neurotoxicity via a neuronal apoptosis mechanism; however, no in vivo research has reported whether ketamine could affect postnatal neurogenesis in the hippocampal dentate gyrus (DG). A growing number of experiments suggest that postnatal hippocampal neurogenesis is the foundation of maintaining normal hippocampus function into adulthood. Therefore, this study investigated the effect of ketamine on hippocampal neurogenesis. Male Sprague-Dawley rats were divided into two groups: the control group (equal volume of normal saline), and the ketamine-anesthesia group (40 mg/kg ketamine in four injections at 1 h intervals). The S-phase marker 5-bromodeoxyuridine (BrdU) was administered after ketamine exposure to postnatal day 7 (PND-7) rats, and the neurogenesis in the hippocampal DG was assessed using single- or double-immunofluorescence staining. The expression of GFAP in the hippocampal DG was measured by western blot analysis. Spatial reference memory was tested by Morris water maze at 2 months after PND-7 rats exposed to ketamine treatment. The present results showed that neonatal ketamine exposure significantly inhibited neural stem cell (NSC) proliferation, decreased astrocytic differentiation, and markedly enhanced neuronal differentiation. The disruptive effect of ketamine on the proliferation and differentiation of NSCs lasted at least 1 week and disappeared by 2 weeks after ketamine exposure. Moreover, the migration of newborn neurons in the granule cell layer and the growth of astrocytes in the hippocampal DG were inhibited by ketamine on PND-37 and PND-44. Finally, ketamine caused a deficit in hippocampal-dependent spatial reference memory tasks at 2 months old. Our results suggested that ketamine may interfere with hippocampal neurogenesis and long-term neurocognitive function in PND-7 rats. These findings may provide a new perspective to explain the adult neurocognitive dysfunction induced by neonatal ketamine exposure. SN - 1476-3524 UR - https://www.unboundmedicine.com/medline/citation/26966008/Ketamine_Affects_the_Neurogenesis_of_the_Hippocampal_Dentate_Gyrus_in_7_Day_Old_Rats_ L2 - https://dx.doi.org/10.1007/s12640-016-9615-7 DB - PRIME DP - Unbound Medicine ER -