Melatonin attenuates sevoflurane-induced hippocampal damage and cognitive deficits in neonatal mice by suppressing CypD in parvalbumin neurons
Background: Sevoflurane, a commonly administered inhaled anesthetic, is found to induce synaptic and mitochondrial damage in neonatal mice. Mitochondrial membrane potential (MMP) changes, mediated by Cyclophilin D (CypD), are implicated in mitochondrial function. Melatonin, known for its significant...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923023002344 |
| _version_ | 1797616024037621760 |
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| author | Xuezhu Zou Xiaoyuan Zhang Tingting Qiang Xianwen Hu Li Zhang |
| author_facet | Xuezhu Zou Xiaoyuan Zhang Tingting Qiang Xianwen Hu Li Zhang |
| author_sort | Xuezhu Zou |
| collection | DOAJ |
| description | Background: Sevoflurane, a commonly administered inhaled anesthetic, is found to induce synaptic and mitochondrial damage in neonatal mice. Mitochondrial membrane potential (MMP) changes, mediated by Cyclophilin D (CypD), are implicated in mitochondrial function. Melatonin, known for its significant neuroprotective properties, was investigated in this study to elucidate its mechanisms in mitigating the cognitive impairment caused by sevoflurane. Methods: The mice were categorized into several groups, including the control, vehicle, sevoflurane, vehicle plus sevoflurane, and melatonin plus sevoflurane groups. From postnatal day 6 to day 8, the mice were administered inhaled sevoflurane or intraperitoneal melatonin. MMP and reactive oxygen species (ROS) were measured using appropriate detection kits. The protein expression levels of PSD95, Synapsin Ⅰ, and CypD in the hippocampus were analyzed through western blotting in acute and prolonged terms. Immunofluorescence staining was used to assess the co-localizations of PSD95 or CypD in parvalbumin (PV) neurons. Cognitive ability was evaluated through novel object recognition, social interaction experiment, and the Morris water maze. Results: The findings revealed that repeated exposure to sevoflurane in neonatal mice resulted in cognitive and synaptic impairment. Furthermore, melatonin administration suppressed the ROS and CypD protein expression, enhanced the MMP in mitochondria and synaptic protein expression in PV neurons, and ameliorated cognitive deficits. Conclusion: Melatonin alleviated sevoflurane-induced cognitive deficits by suppressing CypD and promoting synaptic development in hippocampal PV neurons. These results provide valuable insights into a promising therapeutic approach for preventing neurotoxic injuries caused by general anesthetics. |
| first_indexed | 2024-03-11T07:35:18Z |
| format | Article |
| id | doaj.art-d4db867acd7a49e6b157e63c5b507467 |
| institution | Directory Open Access Journal |
| issn | 1873-2747 |
| language | English |
| last_indexed | 2024-03-11T07:35:18Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj.art-d4db867acd7a49e6b157e63c5b5074672023-11-17T05:25:02ZengElsevierBrain Research Bulletin1873-27472023-11-01204110809Melatonin attenuates sevoflurane-induced hippocampal damage and cognitive deficits in neonatal mice by suppressing CypD in parvalbumin neuronsXuezhu Zou0Xiaoyuan Zhang1Tingting Qiang2Xianwen Hu3Li Zhang4Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei 230061, Anhui Province, China; Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei 230061, Anhui Province, China; Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei 230061, Anhui Province, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei 230061, Anhui Province, China; Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, China; Corresponding authors at: Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei 230061, Anhui Province, China.Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei 230061, Anhui Province, China; Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, China; Corresponding authors at: Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei 230061, Anhui Province, China.Background: Sevoflurane, a commonly administered inhaled anesthetic, is found to induce synaptic and mitochondrial damage in neonatal mice. Mitochondrial membrane potential (MMP) changes, mediated by Cyclophilin D (CypD), are implicated in mitochondrial function. Melatonin, known for its significant neuroprotective properties, was investigated in this study to elucidate its mechanisms in mitigating the cognitive impairment caused by sevoflurane. Methods: The mice were categorized into several groups, including the control, vehicle, sevoflurane, vehicle plus sevoflurane, and melatonin plus sevoflurane groups. From postnatal day 6 to day 8, the mice were administered inhaled sevoflurane or intraperitoneal melatonin. MMP and reactive oxygen species (ROS) were measured using appropriate detection kits. The protein expression levels of PSD95, Synapsin Ⅰ, and CypD in the hippocampus were analyzed through western blotting in acute and prolonged terms. Immunofluorescence staining was used to assess the co-localizations of PSD95 or CypD in parvalbumin (PV) neurons. Cognitive ability was evaluated through novel object recognition, social interaction experiment, and the Morris water maze. Results: The findings revealed that repeated exposure to sevoflurane in neonatal mice resulted in cognitive and synaptic impairment. Furthermore, melatonin administration suppressed the ROS and CypD protein expression, enhanced the MMP in mitochondria and synaptic protein expression in PV neurons, and ameliorated cognitive deficits. Conclusion: Melatonin alleviated sevoflurane-induced cognitive deficits by suppressing CypD and promoting synaptic development in hippocampal PV neurons. These results provide valuable insights into a promising therapeutic approach for preventing neurotoxic injuries caused by general anesthetics.http://www.sciencedirect.com/science/article/pii/S0361923023002344Sevoflurane-induced cognitive deficitsMelatoninSynaptic developmentParvalbumin neuronCyclophilin D |
| spellingShingle | Xuezhu Zou Xiaoyuan Zhang Tingting Qiang Xianwen Hu Li Zhang Melatonin attenuates sevoflurane-induced hippocampal damage and cognitive deficits in neonatal mice by suppressing CypD in parvalbumin neurons Brain Research Bulletin Sevoflurane-induced cognitive deficits Melatonin Synaptic development Parvalbumin neuron Cyclophilin D |
| title | Melatonin attenuates sevoflurane-induced hippocampal damage and cognitive deficits in neonatal mice by suppressing CypD in parvalbumin neurons |
| title_full | Melatonin attenuates sevoflurane-induced hippocampal damage and cognitive deficits in neonatal mice by suppressing CypD in parvalbumin neurons |
| title_fullStr | Melatonin attenuates sevoflurane-induced hippocampal damage and cognitive deficits in neonatal mice by suppressing CypD in parvalbumin neurons |
| title_full_unstemmed | Melatonin attenuates sevoflurane-induced hippocampal damage and cognitive deficits in neonatal mice by suppressing CypD in parvalbumin neurons |
| title_short | Melatonin attenuates sevoflurane-induced hippocampal damage and cognitive deficits in neonatal mice by suppressing CypD in parvalbumin neurons |
| title_sort | melatonin attenuates sevoflurane induced hippocampal damage and cognitive deficits in neonatal mice by suppressing cypd in parvalbumin neurons |
| topic | Sevoflurane-induced cognitive deficits Melatonin Synaptic development Parvalbumin neuron Cyclophilin D |
| url | http://www.sciencedirect.com/science/article/pii/S0361923023002344 |
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