{"title":"异氟醚和聚氨酯对小鼠大脑神经元和星形胶质细胞代谢活性的影响:一项离体1H-[13C]- nmr研究。","authors":"Sreemantula Arun Kumar, Akila Ramesh, Pooja Gautam, Anant Bahadur Patel","doi":"10.1111/bph.70113","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n <h3> Background and Purpose</h3>\n \n <p>Isoflurane and urethane are among the most routinely used anaesthetics to immobilise rodents in functional studies. However, the quantitative significance of their impacts on neuronal and astroglial activity is not very clear. This study evaluated the impacts of isoflurane and urethane on the metabolic activity of glutamatergic neurons, GABAergic neurons and astrocytes in different brain regions.</p>\n </section>\n \n <section>\n \n <h3> Experimental Approach</h3>\n \n <p>Male C57BL/6 mice were anaesthetised with either isoflurane (1.5%) or urethane (1.5 g kg<sup>−1</sup>, intraperitoneal), and administered [1,6-<sup>13</sup>C<sub>2</sub>]glucose or [2-<sup>13</sup>C]acetate intravenously for 10 or 15 min, respectively. The brain metabolism was arrested using Focussed Beam Microwave Irradiation, and the <sup>13</sup>C labelling of neurometabolites in the brain tissue extracts was measured ex vivo using <sup>1</sup>H-[<sup>13</sup>C]-nuclear magnetic resonance (NMR) spectroscopy.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The levels of aspartate and succinate were decreased, while alanine increased in the studied brain regions in mice exposed to isoflurane compared to awake mice. The labelling of Glu<sub>C4/C3</sub>, GABA<sub>C2</sub> and Gln<sub>C4</sub> from [2-<sup>13</sup>C]acetate was decreased in the isoflurane group when compared with awake, suggesting that isoflurane suppresses the astroglial metabolic activity, particularly in the subcortical region. There was a severe reduction in the <sup>13</sup>C labelling of brain amino acids from [1,6-<sup>13</sup>C<sub>2</sub>]glucose in all the brain regions in isoflurane and urethane groups of mice, indicating a severe impact of both anaesthetics on the metabolic activity of glutamatergic and GABAergic neurons.</p>\n </section>\n \n <section>\n \n <h3> Conclusions and Implications</h3>\n \n <p>These findings demonstrate that isoflurane and urethane differentially reduce excitatory and inhibitory synaptic transmissions in the brain. Notably, isoflurane shifts cerebral metabolism towards anaerobic respiration.</p>\n </section>\n </div>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"182 22","pages":"5556-5573"},"PeriodicalIF":7.7000,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Isoflurane and urethane impact neuronal and astroglial metabolic activity differentially in mouse brain: An ex vivo 1H-[13C]-NMR study\",\"authors\":\"Sreemantula Arun Kumar, Akila Ramesh, Pooja Gautam, Anant Bahadur Patel\",\"doi\":\"10.1111/bph.70113\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <section>\\n \\n <h3> Background and Purpose</h3>\\n \\n <p>Isoflurane and urethane are among the most routinely used anaesthetics to immobilise rodents in functional studies. However, the quantitative significance of their impacts on neuronal and astroglial activity is not very clear. This study evaluated the impacts of isoflurane and urethane on the metabolic activity of glutamatergic neurons, GABAergic neurons and astrocytes in different brain regions.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Experimental Approach</h3>\\n \\n <p>Male C57BL/6 mice were anaesthetised with either isoflurane (1.5%) or urethane (1.5 g kg<sup>−1</sup>, intraperitoneal), and administered [1,6-<sup>13</sup>C<sub>2</sub>]glucose or [2-<sup>13</sup>C]acetate intravenously for 10 or 15 min, respectively. The brain metabolism was arrested using Focussed Beam Microwave Irradiation, and the <sup>13</sup>C labelling of neurometabolites in the brain tissue extracts was measured ex vivo using <sup>1</sup>H-[<sup>13</sup>C]-nuclear magnetic resonance (NMR) spectroscopy.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>The levels of aspartate and succinate were decreased, while alanine increased in the studied brain regions in mice exposed to isoflurane compared to awake mice. The labelling of Glu<sub>C4/C3</sub>, GABA<sub>C2</sub> and Gln<sub>C4</sub> from [2-<sup>13</sup>C]acetate was decreased in the isoflurane group when compared with awake, suggesting that isoflurane suppresses the astroglial metabolic activity, particularly in the subcortical region. There was a severe reduction in the <sup>13</sup>C labelling of brain amino acids from [1,6-<sup>13</sup>C<sub>2</sub>]glucose in all the brain regions in isoflurane and urethane groups of mice, indicating a severe impact of both anaesthetics on the metabolic activity of glutamatergic and GABAergic neurons.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions and Implications</h3>\\n \\n <p>These findings demonstrate that isoflurane and urethane differentially reduce excitatory and inhibitory synaptic transmissions in the brain. 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引用次数: 0
摘要
背景和目的:异氟醚和氨基甲酸乙酯是功能研究中最常用的麻醉药。然而,它们对神经元和星形胶质细胞活动的影响的定量意义尚不清楚。本研究探讨了异氟醚和聚氨酯对脑不同区域谷氨酸能神经元、氨基丁酸能神经元和星形胶质细胞代谢活性的影响。实验方法:雄性C57BL/6小鼠分别用异氟烷(1.5%)或氨基甲酸乙酯(1.5 g kg-1,腹腔)麻醉,并静脉注射[1,6- 13c2]葡萄糖或[2-13C]醋酸酯,分别麻醉10 min或15 min。使用聚焦束微波照射捕获脑代谢,并使用1H-[13C]-核磁共振(NMR)波谱法测量脑组织提取物中神经代谢物的13C标记。结果:与清醒小鼠相比,暴露于异氟醚的小鼠脑区天冬氨酸和琥珀酸水平降低,而丙氨酸水平升高。与清醒时相比,异氟醚组[2-13C]醋酸盐标记的GluC4/C3、GABAC2和GlnC4减少,表明异氟醚抑制星形胶质细胞代谢活性,特别是在皮质下区域。在异氟醚和氨基甲酸乙酯组小鼠的所有脑区中,脑氨基酸[1,6- 13c2]葡萄糖的13C标记严重减少,表明麻醉对谷氨酸能和氨基丁酸能神经元的代谢活性有严重影响。结论和意义:这些发现表明异氟醚和聚氨酯在减少大脑兴奋性和抑制性突触传递方面存在差异。值得注意的是,异氟烷使脑代谢转向无氧呼吸。
Isoflurane and urethane impact neuronal and astroglial metabolic activity differentially in mouse brain: An ex vivo 1H-[13C]-NMR study
Background and Purpose
Isoflurane and urethane are among the most routinely used anaesthetics to immobilise rodents in functional studies. However, the quantitative significance of their impacts on neuronal and astroglial activity is not very clear. This study evaluated the impacts of isoflurane and urethane on the metabolic activity of glutamatergic neurons, GABAergic neurons and astrocytes in different brain regions.
Experimental Approach
Male C57BL/6 mice were anaesthetised with either isoflurane (1.5%) or urethane (1.5 g kg−1, intraperitoneal), and administered [1,6-13C2]glucose or [2-13C]acetate intravenously for 10 or 15 min, respectively. The brain metabolism was arrested using Focussed Beam Microwave Irradiation, and the 13C labelling of neurometabolites in the brain tissue extracts was measured ex vivo using 1H-[13C]-nuclear magnetic resonance (NMR) spectroscopy.
Results
The levels of aspartate and succinate were decreased, while alanine increased in the studied brain regions in mice exposed to isoflurane compared to awake mice. The labelling of GluC4/C3, GABAC2 and GlnC4 from [2-13C]acetate was decreased in the isoflurane group when compared with awake, suggesting that isoflurane suppresses the astroglial metabolic activity, particularly in the subcortical region. There was a severe reduction in the 13C labelling of brain amino acids from [1,6-13C2]glucose in all the brain regions in isoflurane and urethane groups of mice, indicating a severe impact of both anaesthetics on the metabolic activity of glutamatergic and GABAergic neurons.
Conclusions and Implications
These findings demonstrate that isoflurane and urethane differentially reduce excitatory and inhibitory synaptic transmissions in the brain. Notably, isoflurane shifts cerebral metabolism towards anaerobic respiration.
期刊介绍:
The British Journal of Pharmacology (BJP) is a biomedical science journal offering comprehensive international coverage of experimental and translational pharmacology. It publishes original research, authoritative reviews, mini reviews, systematic reviews, meta-analyses, databases, letters to the Editor, and commentaries.
Review articles, databases, systematic reviews, and meta-analyses are typically commissioned, but unsolicited contributions are also considered, either as standalone papers or part of themed issues.
In addition to basic science research, BJP features translational pharmacology research, including proof-of-concept and early mechanistic studies in humans. While it generally does not publish first-in-man phase I studies or phase IIb, III, or IV studies, exceptions may be made under certain circumstances, particularly if results are combined with preclinical studies.