The positive allosteric modulation of GABAA receptors mRNA in immature hippocampal rat neurons by midazolam affects receptor expression and induces apoptosis.
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| Title: | The positive allosteric modulation of GABA |
|---|---|
| Authors: | Sinner, Barbara (AUTHOR), Steiner, Julia (AUTHOR), Malsy, Manuela (AUTHOR), Graf, Bernhard M. (AUTHOR), Bundscherer, Anika (AUTHOR) |
| Source: | International Journal of Neuroscience. Oct2019, Vol. 129 Issue 10, p986-994. 9p. |
| Subjects: | Allosteric regulation, Midazolam, Glutamate receptors, AMPA receptors, Neurons, Western immunoblotting |
| Abstract: | Background: Numerous experimental studies show that anesthetics are potentially toxic to the immature brain. Even though benzodiazepines are widely used in pediatric anesthesia and intensive care medicine, only a few studies examine the effects of these drugs on immature neurons. Methods: Hippocampal neuronal cell cultures of embryonic Wistar rats (15 days in culture) were incubated with midazolam 100 or 300 nM for either 30 min or 4 h. The time course of the mRNA expression of the glutamate receptors subunits NR1, NR2A and NR2B of the NMDA receptor, the GluA-1 and A-2 subunits of the AMPA receptor as well as the alpha 1 subunit of the GABAA receptor were examined by PCR. Apoptosis was detected using Western blot analysis for BAX, Bcl-2 and Caspase-3. Results: Midazolam at 100 and 300 nM applied for 30 min and 100 nM for 4 h affected glutamate receptor and GABAA receptor subunit expression. However, these effects were reversible within 72 h following washout. When 300 nM midazolam was applied for 4 h a significant increase in the NR 1 and NR 2A mRNA subunit expression could be detected. The increase in NR 2B receptor subunit expression as well as the GluA1 subunit expression was not reversible within 72 h following washout. This increase in mRNA glutamate receptor subunit expression was associated with a significant increase in neuronal apoptosis. Conclusion: In immature neurons midazolam altered GABA and glutamate mRNA receptor subunit expression. Prolonged increase in midazolam-induced glutamate receptor expression was associated with apoptosis. [ABSTRACT FROM AUTHOR] |
| Copyright of International Journal of Neuroscience is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 138138826 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: The positive allosteric modulation of GABA<subscript>A</subscript> receptors mRNA in immature hippocampal rat neurons by midazolam affects receptor expression and induces apoptosis. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Sinner%2C+Barbara%22">Sinner, Barbara</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Steiner%2C+Julia%22">Steiner, Julia</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Malsy%2C+Manuela%22">Malsy, Manuela</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Graf%2C+Bernhard+M%2E%22">Graf, Bernhard M.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bundscherer%2C+Anika%22">Bundscherer, Anika</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22International+Journal+of+Neuroscience%22">International Journal of Neuroscience</searchLink>. Oct2019, Vol. 129 Issue 10, p986-994. 9p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Allosteric+regulation%22">Allosteric regulation</searchLink><br /><searchLink fieldCode="DE" term="%22Midazolam%22">Midazolam</searchLink><br /><searchLink fieldCode="DE" term="%22Glutamate+receptors%22">Glutamate receptors</searchLink><br /><searchLink fieldCode="DE" term="%22AMPA+receptors%22">AMPA receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Neurons%22">Neurons</searchLink><br /><searchLink fieldCode="DE" term="%22Western+immunoblotting%22">Western immunoblotting</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Background: Numerous experimental studies show that anesthetics are potentially toxic to the immature brain. Even though benzodiazepines are widely used in pediatric anesthesia and intensive care medicine, only a few studies examine the effects of these drugs on immature neurons. Methods: Hippocampal neuronal cell cultures of embryonic Wistar rats (15 days in culture) were incubated with midazolam 100 or 300 nM for either 30 min or 4 h. The time course of the mRNA expression of the glutamate receptors subunits NR1, NR2A and NR2B of the NMDA receptor, the GluA-1 and A-2 subunits of the AMPA receptor as well as the alpha 1 subunit of the GABAA receptor were examined by PCR. Apoptosis was detected using Western blot analysis for BAX, Bcl-2 and Caspase-3. Results: Midazolam at 100 and 300 nM applied for 30 min and 100 nM for 4 h affected glutamate receptor and GABAA receptor subunit expression. However, these effects were reversible within 72 h following washout. When 300 nM midazolam was applied for 4 h a significant increase in the NR 1 and NR 2A mRNA subunit expression could be detected. The increase in NR 2B receptor subunit expression as well as the GluA1 subunit expression was not reversible within 72 h following washout. This increase in mRNA glutamate receptor subunit expression was associated with a significant increase in neuronal apoptosis. Conclusion: In immature neurons midazolam altered GABA and glutamate mRNA receptor subunit expression. Prolonged increase in midazolam-induced glutamate receptor expression was associated with apoptosis. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of International Journal of Neuroscience is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1080/00207454.2019.1604524 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 9 StartPage: 986 Subjects: – SubjectFull: Allosteric regulation Type: general – SubjectFull: Midazolam Type: general – SubjectFull: Glutamate receptors Type: general – SubjectFull: AMPA receptors Type: general – SubjectFull: Neurons Type: general – SubjectFull: Western immunoblotting Type: general Titles: – TitleFull: The positive allosteric modulation of GABAA receptors mRNA in immature hippocampal rat neurons by midazolam affects receptor expression and induces apoptosis. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Sinner, Barbara – PersonEntity: Name: NameFull: Steiner, Julia – PersonEntity: Name: NameFull: Malsy, Manuela – PersonEntity: Name: NameFull: Graf, Bernhard M. – PersonEntity: Name: NameFull: Bundscherer, Anika IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 10 Text: Oct2019 Type: published Y: 2019 Identifiers: – Type: issn-print Value: 00207454 Numbering: – Type: volume Value: 129 – Type: issue Value: 10 Titles: – TitleFull: International Journal of Neuroscience Type: main |
| ResultId | 1 |
