Insulin differentially modulates GABA signalling in hippocampal neurons and, in an age‐dependent manner, normalizes GABA‐activated currents in the tg‐APPSwe mouse model of Alzheimer's disease.
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| Title: | Insulin differentially modulates GABA signalling in hippocampal neurons and, in an age‐dependent manner, normalizes GABA‐activated currents in the tg‐APPSwe mouse model of Alzheimer's disease. |
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| Authors: | Hammoud, Hayma (AUTHOR), Netsyk, Olga (AUTHOR), Tafreshiha, Atieh S. (AUTHOR), Korol, Sergiy V. (AUTHOR), Jin, Zhe (AUTHOR), Li, Jin‐Ping (AUTHOR), Birnir, Bryndis (AUTHOR) |
| Source: | Acta Physiologica. Jun2021, Vol. 232 Issue 2, p1-24. 24p. 1 Color Photograph, 1 Diagram, 8 Graphs. |
| Subjects: | Laboratory mice, Methyl aspartate receptors, Neural transmission, Pyramidal neurons, Inhibitory postsynaptic potential, Granule cells, Alzheimer's disease, Insulin, Dentate gyrus |
| Abstract: | Aim: We examined if tonic γ‐aminobutyric acid (GABA)‐activated currents in primary hippocampal neurons were modulated by insulin in wild‐type and tg‐APPSwe mice, an Alzheimer's disease (AD) model. Methods: GABA‐activated currents were recorded in dentate gyrus (DG) granule cells and CA3 pyramidal neurons in hippocampal brain slices, from 8 to 10 weeks old (young) wild‐type mice and in dorsal DG granule cells in adult, 5‐6 and 10‐12 (aged) months old wild‐type and tg‐APPSwe mice, in the absence or presence of insulin, by whole‐cell patch‐clamp electrophysiology. Results: In young mice, insulin (1 nmol/L) enhanced the total spontaneous inhibitory postsynaptic current (sIPSCT) density in both dorsal and ventral DG granule cells. The extrasynaptic current density was only increased by insulin in dorsal CA3 pyramidal neurons. In absence of action potentials, insulin enhanced DG granule cells and dorsal CA3 pyramidal neurons miniature IPSC (mIPSC) frequency, consistent with insulin regulation of presynaptic GABA release. sIPSCT densities in DG granule cells were similar in wild‐type and tg‐APPSwe mice at 5‐6 months but significantly decreased in aged tg‐APPSwe mice where insulin normalized currents to wild‐type levels. The extrasynaptic current density was increased in tg‐APPSwe mice relative to wild‐type littermates but, only in aged tg‐APPSwe mice did insulin decrease and normalize the current. Conclusion: Insulin effects on GABA signalling in hippocampal neurons are selective while multifaceted and context‐based. Not only is the response to insulin related to cell‐type, hippocampal axis‐location, age of animals and disease but also to the subtype of neuronal inhibition involved, synaptic or extrasynaptic GABAA receptors‐activated currents. [ABSTRACT FROM AUTHOR] |
| Copyright of Acta Physiologica is the property of Wiley-Blackwell 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: 150678644 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Insulin differentially modulates GABA signalling in hippocampal neurons and, in an age‐dependent manner, normalizes GABA‐activated currents in the tg‐APPSwe mouse model of Alzheimer's disease. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Hammoud%2C+Hayma%22">Hammoud, Hayma</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Netsyk%2C+Olga%22">Netsyk, Olga</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Tafreshiha%2C+Atieh+S%2E%22">Tafreshiha, Atieh S.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Korol%2C+Sergiy+V%2E%22">Korol, Sergiy V.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Jin%2C+Zhe%22">Jin, Zhe</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Jin‐Ping%22">Li, Jin‐Ping</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Birnir%2C+Bryndis%22">Birnir, Bryndis</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Acta+Physiologica%22">Acta Physiologica</searchLink>. Jun2021, Vol. 232 Issue 2, p1-24. 24p. 1 Color Photograph, 1 Diagram, 8 Graphs. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Laboratory+mice%22">Laboratory mice</searchLink><br /><searchLink fieldCode="DE" term="%22Methyl+aspartate+receptors%22">Methyl aspartate receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Neural+transmission%22">Neural transmission</searchLink><br /><searchLink fieldCode="DE" term="%22Pyramidal+neurons%22">Pyramidal neurons</searchLink><br /><searchLink fieldCode="DE" term="%22Inhibitory+postsynaptic+potential%22">Inhibitory postsynaptic potential</searchLink><br /><searchLink fieldCode="DE" term="%22Granule+cells%22">Granule cells</searchLink><br /><searchLink fieldCode="DE" term="%22Alzheimer's+disease%22">Alzheimer's disease</searchLink><br /><searchLink fieldCode="DE" term="%22Insulin%22">Insulin</searchLink><br /><searchLink fieldCode="DE" term="%22Dentate+gyrus%22">Dentate gyrus</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Aim: We examined if tonic γ‐aminobutyric acid (GABA)‐activated currents in primary hippocampal neurons were modulated by insulin in wild‐type and tg‐APPSwe mice, an Alzheimer's disease (AD) model. Methods: GABA‐activated currents were recorded in dentate gyrus (DG) granule cells and CA3 pyramidal neurons in hippocampal brain slices, from 8 to 10 weeks old (young) wild‐type mice and in dorsal DG granule cells in adult, 5‐6 and 10‐12 (aged) months old wild‐type and tg‐APPSwe mice, in the absence or presence of insulin, by whole‐cell patch‐clamp electrophysiology. Results: In young mice, insulin (1 nmol/L) enhanced the total spontaneous inhibitory postsynaptic current (sIPSCT) density in both dorsal and ventral DG granule cells. The extrasynaptic current density was only increased by insulin in dorsal CA3 pyramidal neurons. In absence of action potentials, insulin enhanced DG granule cells and dorsal CA3 pyramidal neurons miniature IPSC (mIPSC) frequency, consistent with insulin regulation of presynaptic GABA release. sIPSCT densities in DG granule cells were similar in wild‐type and tg‐APPSwe mice at 5‐6 months but significantly decreased in aged tg‐APPSwe mice where insulin normalized currents to wild‐type levels. The extrasynaptic current density was increased in tg‐APPSwe mice relative to wild‐type littermates but, only in aged tg‐APPSwe mice did insulin decrease and normalize the current. Conclusion: Insulin effects on GABA signalling in hippocampal neurons are selective while multifaceted and context‐based. Not only is the response to insulin related to cell‐type, hippocampal axis‐location, age of animals and disease but also to the subtype of neuronal inhibition involved, synaptic or extrasynaptic GABAA receptors‐activated currents. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Acta Physiologica is the property of Wiley-Blackwell 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.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=150678644 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1111/apha.13623 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 24 StartPage: 1 Subjects: – SubjectFull: Laboratory mice Type: general – SubjectFull: Methyl aspartate receptors Type: general – SubjectFull: Neural transmission Type: general – SubjectFull: Pyramidal neurons Type: general – SubjectFull: Inhibitory postsynaptic potential Type: general – SubjectFull: Granule cells Type: general – SubjectFull: Alzheimer's disease Type: general – SubjectFull: Insulin Type: general – SubjectFull: Dentate gyrus Type: general Titles: – TitleFull: Insulin differentially modulates GABA signalling in hippocampal neurons and, in an age‐dependent manner, normalizes GABA‐activated currents in the tg‐APPSwe mouse model of Alzheimer's disease. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Hammoud, Hayma – PersonEntity: Name: NameFull: Netsyk, Olga – PersonEntity: Name: NameFull: Tafreshiha, Atieh S. – PersonEntity: Name: NameFull: Korol, Sergiy V. – PersonEntity: Name: NameFull: Jin, Zhe – PersonEntity: Name: NameFull: Li, Jin‐Ping – PersonEntity: Name: NameFull: Birnir, Bryndis IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 06 Text: Jun2021 Type: published Y: 2021 Identifiers: – Type: issn-print Value: 17481708 Numbering: – Type: volume Value: 232 – Type: issue Value: 2 Titles: – TitleFull: Acta Physiologica Type: main |
| ResultId | 1 |
