dc.contributor.author |
Vinnakota, Chitra |
en |
dc.contributor.author |
Govindpani, Karan |
en |
dc.contributor.author |
Tate, Warren Perry |
en |
dc.contributor.author |
Peppercorn, Katie |
en |
dc.contributor.author |
Anekal, Praju Vikas |
en |
dc.contributor.author |
Waldvogel, Henry |
en |
dc.contributor.author |
Faull, Richard |
en |
dc.contributor.author |
Kwakowsky, Andrea |
en |
dc.date.accessioned |
2020-07-08T04:45:26Z |
en |
dc.date.issued |
2020-05-06 |
en |
dc.identifier.citation |
International journal of molecular sciences 21(9) 06 May 2020 |
en |
dc.identifier.issn |
1422-0067 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/51963 |
en |
dc.description.abstract |
Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which no cognition-restoring therapies exist. Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. Increasing evidence suggests a remodeling of the GABAergic system in AD, which might represent an important therapeutic target. An inverse agonist of 5 subunit-containing GABAA receptors (α5GABAARs), 3-(5-Methylisoxazol-3-yl)-6-[(1-methyl-1,2,3-triazol-4-yl)methyloxy]-1,2,4-triazolo[3-a]phthalazine (5IA) has cognition-enhancing properties. This study aimed to characterize the effects of 5IA on amyloid beta (A1-42)-induced molecular and cellular changes. Mouse primary hippocampal cultures were exposed to either A1-42 alone, or 5IA alone, 5IA with A1-42 or vehicle alone, and changes in cell viability and mRNA expression of several GABAergic signaling components were assessed. Treatment with 100 nM of 5IA reduced A1-42-induced cell loss by 23.8% (p < 0.0001) after 6 h and by 17.3% after 5 days of treatment (p < 0.0001). Furthermore, we observed an A1-42-induced increase in ambient GABA levels, as well as upregulated mRNA expression of the GABAAR α2,α5,2/3 subunits and the GABABR R1 and R2 subunits. Such changes in GABARs expression could potentially disrupt inhibitory neurotransmission and normal network activity. Treatment with 5IA restored A1-42-induced changes in the expression of α5GABAARs. In summary, this compound might hold neuroprotective potential and represent a new therapeutic avenue for AD. |
en |
dc.format.medium |
Electronic |
en |
dc.language |
eng |
en |
dc.relation.ispartofseries |
International journal of molecular sciences |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
en |
dc.title |
An 5 GABAA Receptor Inverse Agonist, 5IA, Attenuates Amyloid Beta-Induced Neuronal Death in Mouse Hippocampal Cultures. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.3390/ijms21093284 |
en |
pubs.issue |
9 |
en |
pubs.volume |
21 |
en |
dc.rights.holder |
Copyright: The authors |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
research-article |
en |
pubs.subtype |
Journal Article |
en |
pubs.elements-id |
802651 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Anatomy and Medical Imaging |
en |
dc.identifier.eissn |
1422-0067 |
en |
pubs.record-created-at-source-date |
2020-05-10 |
en |
pubs.dimensions-id |
32384683 |
en |