Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior

BackgroundProlonged exposure to general anesthetics during development is known to cause neurobehavioral abnormalities, but the cellular and molecular mechanisms involved are unclear. Microglia are the resident immune cells in the central nervous system and play essential roles in normal brain development.Materials and methodsIn the study, postnatal day 7 (P7) C57BL/6 mice were randomly assigned to two groups. In the sevoflurane (SEVO), mice were exposed to 2.5% sevoflurane for 4 h. In the control group, mice were exposed to carrier gas (30% O2/70% N2) for 4 h. Fixed brain slices from P14 to P21 mice were immunolabeled for ionized calcium-binding adapter molecule 1 (IBA-1) to visualize microglia. The morphological analysis of microglia in the somatosensory cortex was performed using ImageJ and Imaris software. Serial block face scanning electron microscopy (SBF-SEM) was performed to assess the ultrastructure of the microglia and the contacts between microglia and synapse in P14 and P21 mice. The confocal imaging of brain slices was performed to assess microglia surveillance in resting and activated states in P14 and P21 mice. Behavioral tests were used to assess the effect of microglia depletion and repopulation on neurobehavioral abnormalities caused by sevoflurane exposure.ResultsThe prolonged exposure of neonatal mice to sevoflurane induced microglia hyper-ramification with an increase in total branch length, arborization area, and branch complexity 14 days after exposure. Prolonged neonatal sevoflurane exposure reduced contacts between microglia and synapses, without affecting the surveillance of microglia in the resting state or responding to laser-induced focal brain injury. These neonatal changes in microglia were associated with anxiety-like behaviors in adult mice. Furthermore, microglial depletion before sevoflurane exposure and subsequent repopulation in the neonatal brain mitigated anxiety-like behaviors caused by sevoflurane exposure.ConclusionOur experiments indicate that general anesthetics may harm the developing brain, and microglia may be an essential target of general anesthetic-related developmental neurotoxicity. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Hong Li [verfasserIn] Bin Zhou [verfasserIn] Ping Liao [verfasserIn] Daqing Liao [verfasserIn] Linghui Yang [verfasserIn] Jing Wang [verfasserIn] Jin Liu [verfasserIn] Ruotian Jiang [verfasserIn] Lingmin Chen [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	sevoflurane microglia hyper-ramification neuron microglia-synapse contact repopulation

Übergeordnetes Werk:	In: Frontiers in Neurology - Frontiers Media S.A., 2010, 14(2023)
Übergeordnetes Werk:	volume:14 ; year:2023

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fneur.2023.1142739

Katalog-ID:	DOAJ087843633

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245	1	0	\|a Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior
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520			\|a BackgroundProlonged exposure to general anesthetics during development is known to cause neurobehavioral abnormalities, but the cellular and molecular mechanisms involved are unclear. Microglia are the resident immune cells in the central nervous system and play essential roles in normal brain development.Materials and methodsIn the study, postnatal day 7 (P7) C57BL/6 mice were randomly assigned to two groups. In the sevoflurane (SEVO), mice were exposed to 2.5% sevoflurane for 4 h. In the control group, mice were exposed to carrier gas (30% O2/70% N2) for 4 h. Fixed brain slices from P14 to P21 mice were immunolabeled for ionized calcium-binding adapter molecule 1 (IBA-1) to visualize microglia. The morphological analysis of microglia in the somatosensory cortex was performed using ImageJ and Imaris software. Serial block face scanning electron microscopy (SBF-SEM) was performed to assess the ultrastructure of the microglia and the contacts between microglia and synapse in P14 and P21 mice. The confocal imaging of brain slices was performed to assess microglia surveillance in resting and activated states in P14 and P21 mice. Behavioral tests were used to assess the effect of microglia depletion and repopulation on neurobehavioral abnormalities caused by sevoflurane exposure.ResultsThe prolonged exposure of neonatal mice to sevoflurane induced microglia hyper-ramification with an increase in total branch length, arborization area, and branch complexity 14 days after exposure. Prolonged neonatal sevoflurane exposure reduced contacts between microglia and synapses, without affecting the surveillance of microglia in the resting state or responding to laser-induced focal brain injury. These neonatal changes in microglia were associated with anxiety-like behaviors in adult mice. Furthermore, microglial depletion before sevoflurane exposure and subsequent repopulation in the neonatal brain mitigated anxiety-like behaviors caused by sevoflurane exposure.ConclusionOur experiments indicate that general anesthetics may harm the developing brain, and microglia may be an essential target of general anesthetic-related developmental neurotoxicity.
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allfields	10.3389/fneur.2023.1142739 doi (DE-627)DOAJ087843633 (DE-599)DOAJ8b02630fada246b7bb205504ab3956cc DE-627 ger DE-627 rakwb eng RC346-429 Hong Li verfasserin aut Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundProlonged exposure to general anesthetics during development is known to cause neurobehavioral abnormalities, but the cellular and molecular mechanisms involved are unclear. Microglia are the resident immune cells in the central nervous system and play essential roles in normal brain development.Materials and methodsIn the study, postnatal day 7 (P7) C57BL/6 mice were randomly assigned to two groups. In the sevoflurane (SEVO), mice were exposed to 2.5% sevoflurane for 4 h. In the control group, mice were exposed to carrier gas (30% O2/70% N2) for 4 h. Fixed brain slices from P14 to P21 mice were immunolabeled for ionized calcium-binding adapter molecule 1 (IBA-1) to visualize microglia. The morphological analysis of microglia in the somatosensory cortex was performed using ImageJ and Imaris software. Serial block face scanning electron microscopy (SBF-SEM) was performed to assess the ultrastructure of the microglia and the contacts between microglia and synapse in P14 and P21 mice. The confocal imaging of brain slices was performed to assess microglia surveillance in resting and activated states in P14 and P21 mice. Behavioral tests were used to assess the effect of microglia depletion and repopulation on neurobehavioral abnormalities caused by sevoflurane exposure.ResultsThe prolonged exposure of neonatal mice to sevoflurane induced microglia hyper-ramification with an increase in total branch length, arborization area, and branch complexity 14 days after exposure. Prolonged neonatal sevoflurane exposure reduced contacts between microglia and synapses, without affecting the surveillance of microglia in the resting state or responding to laser-induced focal brain injury. These neonatal changes in microglia were associated with anxiety-like behaviors in adult mice. Furthermore, microglial depletion before sevoflurane exposure and subsequent repopulation in the neonatal brain mitigated anxiety-like behaviors caused by sevoflurane exposure.ConclusionOur experiments indicate that general anesthetics may harm the developing brain, and microglia may be an essential target of general anesthetic-related developmental neurotoxicity. sevoflurane microglia hyper-ramification neuron microglia-synapse contact repopulation Neurology. Diseases of the nervous system Hong Li verfasserin aut Bin Zhou verfasserin aut Bin Zhou verfasserin aut Ping Liao verfasserin aut Daqing Liao verfasserin aut Linghui Yang verfasserin aut Jing Wang verfasserin aut Jin Liu verfasserin aut Jin Liu verfasserin aut Ruotian Jiang verfasserin aut Ruotian Jiang verfasserin aut Lingmin Chen verfasserin aut Lingmin Chen verfasserin aut In Frontiers in Neurology Frontiers Media S.A., 2010 14(2023) (DE-627)631498753 (DE-600)2564214-5 16642295 nnns volume:14 year:2023 https://doi.org/10.3389/fneur.2023.1142739 kostenfrei https://doaj.org/article/8b02630fada246b7bb205504ab3956cc kostenfrei https://www.frontiersin.org/articles/10.3389/fneur.2023.1142739/full kostenfrei https://doaj.org/toc/1664-2295 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023
spelling	10.3389/fneur.2023.1142739 doi (DE-627)DOAJ087843633 (DE-599)DOAJ8b02630fada246b7bb205504ab3956cc DE-627 ger DE-627 rakwb eng RC346-429 Hong Li verfasserin aut Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundProlonged exposure to general anesthetics during development is known to cause neurobehavioral abnormalities, but the cellular and molecular mechanisms involved are unclear. Microglia are the resident immune cells in the central nervous system and play essential roles in normal brain development.Materials and methodsIn the study, postnatal day 7 (P7) C57BL/6 mice were randomly assigned to two groups. In the sevoflurane (SEVO), mice were exposed to 2.5% sevoflurane for 4 h. In the control group, mice were exposed to carrier gas (30% O2/70% N2) for 4 h. Fixed brain slices from P14 to P21 mice were immunolabeled for ionized calcium-binding adapter molecule 1 (IBA-1) to visualize microglia. The morphological analysis of microglia in the somatosensory cortex was performed using ImageJ and Imaris software. Serial block face scanning electron microscopy (SBF-SEM) was performed to assess the ultrastructure of the microglia and the contacts between microglia and synapse in P14 and P21 mice. The confocal imaging of brain slices was performed to assess microglia surveillance in resting and activated states in P14 and P21 mice. Behavioral tests were used to assess the effect of microglia depletion and repopulation on neurobehavioral abnormalities caused by sevoflurane exposure.ResultsThe prolonged exposure of neonatal mice to sevoflurane induced microglia hyper-ramification with an increase in total branch length, arborization area, and branch complexity 14 days after exposure. Prolonged neonatal sevoflurane exposure reduced contacts between microglia and synapses, without affecting the surveillance of microglia in the resting state or responding to laser-induced focal brain injury. These neonatal changes in microglia were associated with anxiety-like behaviors in adult mice. Furthermore, microglial depletion before sevoflurane exposure and subsequent repopulation in the neonatal brain mitigated anxiety-like behaviors caused by sevoflurane exposure.ConclusionOur experiments indicate that general anesthetics may harm the developing brain, and microglia may be an essential target of general anesthetic-related developmental neurotoxicity. sevoflurane microglia hyper-ramification neuron microglia-synapse contact repopulation Neurology. Diseases of the nervous system Hong Li verfasserin aut Bin Zhou verfasserin aut Bin Zhou verfasserin aut Ping Liao verfasserin aut Daqing Liao verfasserin aut Linghui Yang verfasserin aut Jing Wang verfasserin aut Jin Liu verfasserin aut Jin Liu verfasserin aut Ruotian Jiang verfasserin aut Ruotian Jiang verfasserin aut Lingmin Chen verfasserin aut Lingmin Chen verfasserin aut In Frontiers in Neurology Frontiers Media S.A., 2010 14(2023) (DE-627)631498753 (DE-600)2564214-5 16642295 nnns volume:14 year:2023 https://doi.org/10.3389/fneur.2023.1142739 kostenfrei https://doaj.org/article/8b02630fada246b7bb205504ab3956cc kostenfrei https://www.frontiersin.org/articles/10.3389/fneur.2023.1142739/full kostenfrei https://doaj.org/toc/1664-2295 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023
allfields_unstemmed	10.3389/fneur.2023.1142739 doi (DE-627)DOAJ087843633 (DE-599)DOAJ8b02630fada246b7bb205504ab3956cc DE-627 ger DE-627 rakwb eng RC346-429 Hong Li verfasserin aut Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundProlonged exposure to general anesthetics during development is known to cause neurobehavioral abnormalities, but the cellular and molecular mechanisms involved are unclear. Microglia are the resident immune cells in the central nervous system and play essential roles in normal brain development.Materials and methodsIn the study, postnatal day 7 (P7) C57BL/6 mice were randomly assigned to two groups. In the sevoflurane (SEVO), mice were exposed to 2.5% sevoflurane for 4 h. In the control group, mice were exposed to carrier gas (30% O2/70% N2) for 4 h. Fixed brain slices from P14 to P21 mice were immunolabeled for ionized calcium-binding adapter molecule 1 (IBA-1) to visualize microglia. The morphological analysis of microglia in the somatosensory cortex was performed using ImageJ and Imaris software. Serial block face scanning electron microscopy (SBF-SEM) was performed to assess the ultrastructure of the microglia and the contacts between microglia and synapse in P14 and P21 mice. The confocal imaging of brain slices was performed to assess microglia surveillance in resting and activated states in P14 and P21 mice. Behavioral tests were used to assess the effect of microglia depletion and repopulation on neurobehavioral abnormalities caused by sevoflurane exposure.ResultsThe prolonged exposure of neonatal mice to sevoflurane induced microglia hyper-ramification with an increase in total branch length, arborization area, and branch complexity 14 days after exposure. Prolonged neonatal sevoflurane exposure reduced contacts between microglia and synapses, without affecting the surveillance of microglia in the resting state or responding to laser-induced focal brain injury. These neonatal changes in microglia were associated with anxiety-like behaviors in adult mice. Furthermore, microglial depletion before sevoflurane exposure and subsequent repopulation in the neonatal brain mitigated anxiety-like behaviors caused by sevoflurane exposure.ConclusionOur experiments indicate that general anesthetics may harm the developing brain, and microglia may be an essential target of general anesthetic-related developmental neurotoxicity. sevoflurane microglia hyper-ramification neuron microglia-synapse contact repopulation Neurology. Diseases of the nervous system Hong Li verfasserin aut Bin Zhou verfasserin aut Bin Zhou verfasserin aut Ping Liao verfasserin aut Daqing Liao verfasserin aut Linghui Yang verfasserin aut Jing Wang verfasserin aut Jin Liu verfasserin aut Jin Liu verfasserin aut Ruotian Jiang verfasserin aut Ruotian Jiang verfasserin aut Lingmin Chen verfasserin aut Lingmin Chen verfasserin aut In Frontiers in Neurology Frontiers Media S.A., 2010 14(2023) (DE-627)631498753 (DE-600)2564214-5 16642295 nnns volume:14 year:2023 https://doi.org/10.3389/fneur.2023.1142739 kostenfrei https://doaj.org/article/8b02630fada246b7bb205504ab3956cc kostenfrei https://www.frontiersin.org/articles/10.3389/fneur.2023.1142739/full kostenfrei https://doaj.org/toc/1664-2295 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023
allfieldsGer	10.3389/fneur.2023.1142739 doi (DE-627)DOAJ087843633 (DE-599)DOAJ8b02630fada246b7bb205504ab3956cc DE-627 ger DE-627 rakwb eng RC346-429 Hong Li verfasserin aut Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundProlonged exposure to general anesthetics during development is known to cause neurobehavioral abnormalities, but the cellular and molecular mechanisms involved are unclear. Microglia are the resident immune cells in the central nervous system and play essential roles in normal brain development.Materials and methodsIn the study, postnatal day 7 (P7) C57BL/6 mice were randomly assigned to two groups. In the sevoflurane (SEVO), mice were exposed to 2.5% sevoflurane for 4 h. In the control group, mice were exposed to carrier gas (30% O2/70% N2) for 4 h. Fixed brain slices from P14 to P21 mice were immunolabeled for ionized calcium-binding adapter molecule 1 (IBA-1) to visualize microglia. The morphological analysis of microglia in the somatosensory cortex was performed using ImageJ and Imaris software. Serial block face scanning electron microscopy (SBF-SEM) was performed to assess the ultrastructure of the microglia and the contacts between microglia and synapse in P14 and P21 mice. The confocal imaging of brain slices was performed to assess microglia surveillance in resting and activated states in P14 and P21 mice. Behavioral tests were used to assess the effect of microglia depletion and repopulation on neurobehavioral abnormalities caused by sevoflurane exposure.ResultsThe prolonged exposure of neonatal mice to sevoflurane induced microglia hyper-ramification with an increase in total branch length, arborization area, and branch complexity 14 days after exposure. Prolonged neonatal sevoflurane exposure reduced contacts between microglia and synapses, without affecting the surveillance of microglia in the resting state or responding to laser-induced focal brain injury. These neonatal changes in microglia were associated with anxiety-like behaviors in adult mice. Furthermore, microglial depletion before sevoflurane exposure and subsequent repopulation in the neonatal brain mitigated anxiety-like behaviors caused by sevoflurane exposure.ConclusionOur experiments indicate that general anesthetics may harm the developing brain, and microglia may be an essential target of general anesthetic-related developmental neurotoxicity. sevoflurane microglia hyper-ramification neuron microglia-synapse contact repopulation Neurology. Diseases of the nervous system Hong Li verfasserin aut Bin Zhou verfasserin aut Bin Zhou verfasserin aut Ping Liao verfasserin aut Daqing Liao verfasserin aut Linghui Yang verfasserin aut Jing Wang verfasserin aut Jin Liu verfasserin aut Jin Liu verfasserin aut Ruotian Jiang verfasserin aut Ruotian Jiang verfasserin aut Lingmin Chen verfasserin aut Lingmin Chen verfasserin aut In Frontiers in Neurology Frontiers Media S.A., 2010 14(2023) (DE-627)631498753 (DE-600)2564214-5 16642295 nnns volume:14 year:2023 https://doi.org/10.3389/fneur.2023.1142739 kostenfrei https://doaj.org/article/8b02630fada246b7bb205504ab3956cc kostenfrei https://www.frontiersin.org/articles/10.3389/fneur.2023.1142739/full kostenfrei https://doaj.org/toc/1664-2295 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023
allfieldsSound	10.3389/fneur.2023.1142739 doi (DE-627)DOAJ087843633 (DE-599)DOAJ8b02630fada246b7bb205504ab3956cc DE-627 ger DE-627 rakwb eng RC346-429 Hong Li verfasserin aut Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundProlonged exposure to general anesthetics during development is known to cause neurobehavioral abnormalities, but the cellular and molecular mechanisms involved are unclear. Microglia are the resident immune cells in the central nervous system and play essential roles in normal brain development.Materials and methodsIn the study, postnatal day 7 (P7) C57BL/6 mice were randomly assigned to two groups. In the sevoflurane (SEVO), mice were exposed to 2.5% sevoflurane for 4 h. In the control group, mice were exposed to carrier gas (30% O2/70% N2) for 4 h. Fixed brain slices from P14 to P21 mice were immunolabeled for ionized calcium-binding adapter molecule 1 (IBA-1) to visualize microglia. The morphological analysis of microglia in the somatosensory cortex was performed using ImageJ and Imaris software. Serial block face scanning electron microscopy (SBF-SEM) was performed to assess the ultrastructure of the microglia and the contacts between microglia and synapse in P14 and P21 mice. The confocal imaging of brain slices was performed to assess microglia surveillance in resting and activated states in P14 and P21 mice. Behavioral tests were used to assess the effect of microglia depletion and repopulation on neurobehavioral abnormalities caused by sevoflurane exposure.ResultsThe prolonged exposure of neonatal mice to sevoflurane induced microglia hyper-ramification with an increase in total branch length, arborization area, and branch complexity 14 days after exposure. Prolonged neonatal sevoflurane exposure reduced contacts between microglia and synapses, without affecting the surveillance of microglia in the resting state or responding to laser-induced focal brain injury. These neonatal changes in microglia were associated with anxiety-like behaviors in adult mice. Furthermore, microglial depletion before sevoflurane exposure and subsequent repopulation in the neonatal brain mitigated anxiety-like behaviors caused by sevoflurane exposure.ConclusionOur experiments indicate that general anesthetics may harm the developing brain, and microglia may be an essential target of general anesthetic-related developmental neurotoxicity. sevoflurane microglia hyper-ramification neuron microglia-synapse contact repopulation Neurology. Diseases of the nervous system Hong Li verfasserin aut Bin Zhou verfasserin aut Bin Zhou verfasserin aut Ping Liao verfasserin aut Daqing Liao verfasserin aut Linghui Yang verfasserin aut Jing Wang verfasserin aut Jin Liu verfasserin aut Jin Liu verfasserin aut Ruotian Jiang verfasserin aut Ruotian Jiang verfasserin aut Lingmin Chen verfasserin aut Lingmin Chen verfasserin aut In Frontiers in Neurology Frontiers Media S.A., 2010 14(2023) (DE-627)631498753 (DE-600)2564214-5 16642295 nnns volume:14 year:2023 https://doi.org/10.3389/fneur.2023.1142739 kostenfrei https://doaj.org/article/8b02630fada246b7bb205504ab3956cc kostenfrei https://www.frontiersin.org/articles/10.3389/fneur.2023.1142739/full kostenfrei https://doaj.org/toc/1664-2295 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023
language	English
source	In Frontiers in Neurology 14(2023) volume:14 year:2023
sourceStr	In Frontiers in Neurology 14(2023) volume:14 year:2023
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	sevoflurane microglia hyper-ramification neuron microglia-synapse contact repopulation Neurology. Diseases of the nervous system
isfreeaccess_bool	true
container_title	Frontiers in Neurology
authorswithroles_txt_mv	Hong Li @@aut@@ Bin Zhou @@aut@@ Ping Liao @@aut@@ Daqing Liao @@aut@@ Linghui Yang @@aut@@ Jing Wang @@aut@@ Jin Liu @@aut@@ Ruotian Jiang @@aut@@ Lingmin Chen @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	631498753
id	DOAJ087843633
language_de	englisch
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Microglia are the resident immune cells in the central nervous system and play essential roles in normal brain development.Materials and methodsIn the study, postnatal day 7 (P7) C57BL/6 mice were randomly assigned to two groups. In the sevoflurane (SEVO), mice were exposed to 2.5% sevoflurane for 4 h. In the control group, mice were exposed to carrier gas (30% O2/70% N2) for 4 h. Fixed brain slices from P14 to P21 mice were immunolabeled for ionized calcium-binding adapter molecule 1 (IBA-1) to visualize microglia. The morphological analysis of microglia in the somatosensory cortex was performed using ImageJ and Imaris software. Serial block face scanning electron microscopy (SBF-SEM) was performed to assess the ultrastructure of the microglia and the contacts between microglia and synapse in P14 and P21 mice. The confocal imaging of brain slices was performed to assess microglia surveillance in resting and activated states in P14 and P21 mice. Behavioral tests were used to assess the effect of microglia depletion and repopulation on neurobehavioral abnormalities caused by sevoflurane exposure.ResultsThe prolonged exposure of neonatal mice to sevoflurane induced microglia hyper-ramification with an increase in total branch length, arborization area, and branch complexity 14 days after exposure. Prolonged neonatal sevoflurane exposure reduced contacts between microglia and synapses, without affecting the surveillance of microglia in the resting state or responding to laser-induced focal brain injury. These neonatal changes in microglia were associated with anxiety-like behaviors in adult mice. Furthermore, microglial depletion before sevoflurane exposure and subsequent repopulation in the neonatal brain mitigated anxiety-like behaviors caused by sevoflurane exposure.ConclusionOur experiments indicate that general anesthetics may harm the developing brain, and microglia may be an essential target of general anesthetic-related developmental neurotoxicity.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">sevoflurane</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">microglia</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">hyper-ramification</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">neuron</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">microglia-synapse contact</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">repopulation</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Neurology. 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callnumber-first	R - Medicine
author	Hong Li
spellingShingle	Hong Li misc RC346-429 misc sevoflurane misc microglia misc hyper-ramification misc neuron misc microglia-synapse contact misc repopulation misc Neurology. Diseases of the nervous system Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior
authorStr	Hong Li
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topic_title	RC346-429 Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior sevoflurane microglia hyper-ramification neuron microglia-synapse contact repopulation
topic	misc RC346-429 misc sevoflurane misc microglia misc hyper-ramification misc neuron misc microglia-synapse contact misc repopulation misc Neurology. Diseases of the nervous system
topic_unstemmed	misc RC346-429 misc sevoflurane misc microglia misc hyper-ramification misc neuron misc microglia-synapse contact misc repopulation misc Neurology. Diseases of the nervous system
topic_browse	misc RC346-429 misc sevoflurane misc microglia misc hyper-ramification misc neuron misc microglia-synapse contact misc repopulation misc Neurology. Diseases of the nervous system
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title	Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior
ctrlnum	(DE-627)DOAJ087843633 (DE-599)DOAJ8b02630fada246b7bb205504ab3956cc
title_full	Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior
author_sort	Hong Li
journal	Frontiers in Neurology
journalStr	Frontiers in Neurology
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author_browse	Hong Li Bin Zhou Ping Liao Daqing Liao Linghui Yang Jing Wang Jin Liu Ruotian Jiang Lingmin Chen
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doi_str_mv	10.3389/fneur.2023.1142739
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title_sort	prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior
callnumber	RC346-429
title_auth	Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior
abstract	BackgroundProlonged exposure to general anesthetics during development is known to cause neurobehavioral abnormalities, but the cellular and molecular mechanisms involved are unclear. Microglia are the resident immune cells in the central nervous system and play essential roles in normal brain development.Materials and methodsIn the study, postnatal day 7 (P7) C57BL/6 mice were randomly assigned to two groups. In the sevoflurane (SEVO), mice were exposed to 2.5% sevoflurane for 4 h. In the control group, mice were exposed to carrier gas (30% O2/70% N2) for 4 h. Fixed brain slices from P14 to P21 mice were immunolabeled for ionized calcium-binding adapter molecule 1 (IBA-1) to visualize microglia. The morphological analysis of microglia in the somatosensory cortex was performed using ImageJ and Imaris software. Serial block face scanning electron microscopy (SBF-SEM) was performed to assess the ultrastructure of the microglia and the contacts between microglia and synapse in P14 and P21 mice. The confocal imaging of brain slices was performed to assess microglia surveillance in resting and activated states in P14 and P21 mice. Behavioral tests were used to assess the effect of microglia depletion and repopulation on neurobehavioral abnormalities caused by sevoflurane exposure.ResultsThe prolonged exposure of neonatal mice to sevoflurane induced microglia hyper-ramification with an increase in total branch length, arborization area, and branch complexity 14 days after exposure. Prolonged neonatal sevoflurane exposure reduced contacts between microglia and synapses, without affecting the surveillance of microglia in the resting state or responding to laser-induced focal brain injury. These neonatal changes in microglia were associated with anxiety-like behaviors in adult mice. Furthermore, microglial depletion before sevoflurane exposure and subsequent repopulation in the neonatal brain mitigated anxiety-like behaviors caused by sevoflurane exposure.ConclusionOur experiments indicate that general anesthetics may harm the developing brain, and microglia may be an essential target of general anesthetic-related developmental neurotoxicity.
abstractGer	BackgroundProlonged exposure to general anesthetics during development is known to cause neurobehavioral abnormalities, but the cellular and molecular mechanisms involved are unclear. Microglia are the resident immune cells in the central nervous system and play essential roles in normal brain development.Materials and methodsIn the study, postnatal day 7 (P7) C57BL/6 mice were randomly assigned to two groups. In the sevoflurane (SEVO), mice were exposed to 2.5% sevoflurane for 4 h. In the control group, mice were exposed to carrier gas (30% O2/70% N2) for 4 h. Fixed brain slices from P14 to P21 mice were immunolabeled for ionized calcium-binding adapter molecule 1 (IBA-1) to visualize microglia. The morphological analysis of microglia in the somatosensory cortex was performed using ImageJ and Imaris software. Serial block face scanning electron microscopy (SBF-SEM) was performed to assess the ultrastructure of the microglia and the contacts between microglia and synapse in P14 and P21 mice. The confocal imaging of brain slices was performed to assess microglia surveillance in resting and activated states in P14 and P21 mice. Behavioral tests were used to assess the effect of microglia depletion and repopulation on neurobehavioral abnormalities caused by sevoflurane exposure.ResultsThe prolonged exposure of neonatal mice to sevoflurane induced microglia hyper-ramification with an increase in total branch length, arborization area, and branch complexity 14 days after exposure. Prolonged neonatal sevoflurane exposure reduced contacts between microglia and synapses, without affecting the surveillance of microglia in the resting state or responding to laser-induced focal brain injury. These neonatal changes in microglia were associated with anxiety-like behaviors in adult mice. Furthermore, microglial depletion before sevoflurane exposure and subsequent repopulation in the neonatal brain mitigated anxiety-like behaviors caused by sevoflurane exposure.ConclusionOur experiments indicate that general anesthetics may harm the developing brain, and microglia may be an essential target of general anesthetic-related developmental neurotoxicity.
abstract_unstemmed	BackgroundProlonged exposure to general anesthetics during development is known to cause neurobehavioral abnormalities, but the cellular and molecular mechanisms involved are unclear. Microglia are the resident immune cells in the central nervous system and play essential roles in normal brain development.Materials and methodsIn the study, postnatal day 7 (P7) C57BL/6 mice were randomly assigned to two groups. In the sevoflurane (SEVO), mice were exposed to 2.5% sevoflurane for 4 h. In the control group, mice were exposed to carrier gas (30% O2/70% N2) for 4 h. Fixed brain slices from P14 to P21 mice were immunolabeled for ionized calcium-binding adapter molecule 1 (IBA-1) to visualize microglia. The morphological analysis of microglia in the somatosensory cortex was performed using ImageJ and Imaris software. Serial block face scanning electron microscopy (SBF-SEM) was performed to assess the ultrastructure of the microglia and the contacts between microglia and synapse in P14 and P21 mice. The confocal imaging of brain slices was performed to assess microglia surveillance in resting and activated states in P14 and P21 mice. Behavioral tests were used to assess the effect of microglia depletion and repopulation on neurobehavioral abnormalities caused by sevoflurane exposure.ResultsThe prolonged exposure of neonatal mice to sevoflurane induced microglia hyper-ramification with an increase in total branch length, arborization area, and branch complexity 14 days after exposure. Prolonged neonatal sevoflurane exposure reduced contacts between microglia and synapses, without affecting the surveillance of microglia in the resting state or responding to laser-induced focal brain injury. These neonatal changes in microglia were associated with anxiety-like behaviors in adult mice. Furthermore, microglial depletion before sevoflurane exposure and subsequent repopulation in the neonatal brain mitigated anxiety-like behaviors caused by sevoflurane exposure.ConclusionOur experiments indicate that general anesthetics may harm the developing brain, and microglia may be an essential target of general anesthetic-related developmental neurotoxicity.
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title_short	Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior
url	https://doi.org/10.3389/fneur.2023.1142739 https://doaj.org/article/8b02630fada246b7bb205504ab3956cc https://www.frontiersin.org/articles/10.3389/fneur.2023.1142739/full https://doaj.org/toc/1664-2295
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author2	Hong Li Bin Zhou Ping Liao Daqing Liao Linghui Yang Jing Wang Jin Liu Ruotian Jiang Lingmin Chen
author2Str	Hong Li Bin Zhou Ping Liao Daqing Liao Linghui Yang Jing Wang Jin Liu Ruotian Jiang Lingmin Chen
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doi_str	10.3389/fneur.2023.1142739
callnumber-a	RC346-429
up_date	2024-07-03T14:17:28.159Z
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Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior

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