Ketamine affects the integration of developmentally generated granule neurons in the adult stage
Abstract Background Ketamine has been reported to cause neonatal neurotoxicity in a variety of developing animal models. Various studies have been conducted to study the mechanism of neurotoxicity for general anesthetic use during the neonatal period. Previous experiments have suggested that develop...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-12-01
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| Series: | BMC Neuroscience |
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| Online Access: | https://doi.org/10.1186/s12868-019-0542-4 |
| _version_ | 1818449917009461248 |
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| author | Zhanqiang Zhao Bing Li Yuqing Wu Xujun Chen Yan Guo Yang Shen He Huang |
| author_facet | Zhanqiang Zhao Bing Li Yuqing Wu Xujun Chen Yan Guo Yang Shen He Huang |
| author_sort | Zhanqiang Zhao |
| collection | DOAJ |
| description | Abstract Background Ketamine has been reported to cause neonatal neurotoxicity in a variety of developing animal models. Various studies have been conducted to study the mechanism of neurotoxicity for general anesthetic use during the neonatal period. Previous experiments have suggested that developmentally generated granule neurons in the hippocampus dentate gyrus (DG) supported hippocampus-dependent memory. Therefore, this study aimed to investigate whether ketamine affects the functional integration of developmentally generated granule neurons in the DG. For this purpose,the postnatal day 7 (PND-7) Sprague-Dawley (SD) rats were divided into the control group and the ketamine group (rats who received 4 injections of 40 mg/kg ketamine at 1 h intervals). To label dividing cells, BrdU was administered for three consecutive days after the ketamine exposure; NeuN+/BrdU+cells were observed by using immunofluorescence. To evaluate the developmentally generated granule neurons that support hippocampus-dependent memory, spatial reference memory was tested by using Morris Water Maze at 3 months old, after which the immunofluorescence was used to detect c-Fos expression in the NeuN+/BrdU+ cells. The expression of caspase-3 was measured by western blot to detect the apoptosis in the hippocampal DG. Results The present results showed that the neonatal ketamine exposure did not influence the survival rate of developmentally generated granule neurons at 2 and 3 months old, but ketamine interfered with the integration of these neurons into the hippocampal DG neural circuits and caused a deficit in hippocampal-dependent spatial reference memory tasks. Conclusions In summary, these findings may promote more studies to investigate the neurotoxicity of ketamine in the developing brain. |
| first_indexed | 2024-12-14T20:43:01Z |
| format | Article |
| id | doaj.art-cd696343d80c4c9783a074b6cc6fdeaa |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-12-14T20:43:01Z |
| publishDate | 2019-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-cd696343d80c4c9783a074b6cc6fdeaa2022-12-21T22:48:11ZengBMCBMC Neuroscience1471-22022019-12-0120111010.1186/s12868-019-0542-4Ketamine affects the integration of developmentally generated granule neurons in the adult stageZhanqiang Zhao0Bing Li1Yuqing Wu2Xujun Chen3Yan Guo4Yang Shen5He Huang6Department of Anesthesiology, Jiangning Hospital of Traditional Chinese MedicineDepartment of Anesthesiology, Jiangning Hospital of Traditional Chinese MedicineJiangsu Province Key Laboratory of AnesthesiologyDepartment of Anesthesiology, Jiangning Hospital of Traditional Chinese MedicineDepartment of Anesthesiology, Jiangning Hospital of Traditional Chinese MedicineDepartment of Anesthesiology, Jiangning Hospital of Traditional Chinese MedicineDepartment of Anesthesiology, First Affiliated Hospital With Nanjing Medical UniversityAbstract Background Ketamine has been reported to cause neonatal neurotoxicity in a variety of developing animal models. Various studies have been conducted to study the mechanism of neurotoxicity for general anesthetic use during the neonatal period. Previous experiments have suggested that developmentally generated granule neurons in the hippocampus dentate gyrus (DG) supported hippocampus-dependent memory. Therefore, this study aimed to investigate whether ketamine affects the functional integration of developmentally generated granule neurons in the DG. For this purpose,the postnatal day 7 (PND-7) Sprague-Dawley (SD) rats were divided into the control group and the ketamine group (rats who received 4 injections of 40 mg/kg ketamine at 1 h intervals). To label dividing cells, BrdU was administered for three consecutive days after the ketamine exposure; NeuN+/BrdU+cells were observed by using immunofluorescence. To evaluate the developmentally generated granule neurons that support hippocampus-dependent memory, spatial reference memory was tested by using Morris Water Maze at 3 months old, after which the immunofluorescence was used to detect c-Fos expression in the NeuN+/BrdU+ cells. The expression of caspase-3 was measured by western blot to detect the apoptosis in the hippocampal DG. Results The present results showed that the neonatal ketamine exposure did not influence the survival rate of developmentally generated granule neurons at 2 and 3 months old, but ketamine interfered with the integration of these neurons into the hippocampal DG neural circuits and caused a deficit in hippocampal-dependent spatial reference memory tasks. Conclusions In summary, these findings may promote more studies to investigate the neurotoxicity of ketamine in the developing brain.https://doi.org/10.1186/s12868-019-0542-4KetamineDentate gyrusFunctional integrationNeural circuitsMorris water mazeLearning |
| spellingShingle | Zhanqiang Zhao Bing Li Yuqing Wu Xujun Chen Yan Guo Yang Shen He Huang Ketamine affects the integration of developmentally generated granule neurons in the adult stage BMC Neuroscience Ketamine Dentate gyrus Functional integration Neural circuits Morris water maze Learning |
| title | Ketamine affects the integration of developmentally generated granule neurons in the adult stage |
| title_full | Ketamine affects the integration of developmentally generated granule neurons in the adult stage |
| title_fullStr | Ketamine affects the integration of developmentally generated granule neurons in the adult stage |
| title_full_unstemmed | Ketamine affects the integration of developmentally generated granule neurons in the adult stage |
| title_short | Ketamine affects the integration of developmentally generated granule neurons in the adult stage |
| title_sort | ketamine affects the integration of developmentally generated granule neurons in the adult stage |
| topic | Ketamine Dentate gyrus Functional integration Neural circuits Morris water maze Learning |
| url | https://doi.org/10.1186/s12868-019-0542-4 |
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