Procognitive and neurotrophic benefits of α5-GABA-A receptor positive allosteric modulation in a β-amyloid deposition mouse model of Alzheimer’s disease pathology Article Swipe
Ashley Bernardo
,
Michael Marcotte
,
Kayla Wong
,
Dishary Sharmin
,
Kamal Prakash Pandey
,
James M. Cook
,
Etienne Sibille
,
Thomas D. Prévot
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1016/j.neurobiolaging.2024.12.001
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1016/j.neurobiolaging.2024.12.001
Reduced somatostatin (SST) and SST-expressing GABAergic neurons are well-replicated findings in Alzheimer's disease (AD) and are associated with cognitive deficits. SST cells inhibit pyramidal cell dendrites through α5-GABA-A receptors (α5-GABAA-R). α5-GABAAR positive allosteric modulation (α5-PAM) has procognitive and neurotrophic effects in stress and aging models. We tested whether α5-PAM (GL-II-73) could prevent cognitive deficits and neuronal spine loss in early stages, and reverse them in late stages of β-amyloid deposition in the 5xFAD model (N = 48/study; 50 % female). Acute administration of GL-II-73 prevented spatial working memory deficits in 5xFAD mice at 2 months of age, while chronic administration reversed the deficits at 5 months of age. Chronic GL-II-73 treatment prevented 5xFAD-induced loss of spine density, spine count and dendritic length at both time points, despite β-amyloid accumulation. These results demonstrate procognitive and neurotrophic effects of GL-II-73 in early and late stages of Alzheimer-related β-amyloid deposition. This suggests α5-PAM as a novel β-amyloid-independent symptomatic therapeutic approach.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.neurobiolaging.2024.12.001
- OA Status
- hybrid
- Cited By
- 5
- References
- 74
- Related Works
- 10
- OpenAlex ID
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All OpenAlex metadata
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https://openalex.org/W4405237259Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1016/j.neurobiolaging.2024.12.001Digital Object Identifier
- Title
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Procognitive and neurotrophic benefits of α5-GABA-A receptor positive allosteric modulation in a β-amyloid deposition mouse model of Alzheimer’s disease pathologyWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2024Year of publication
- Publication date
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2024-12-10Full publication date if available
- Authors
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Ashley Bernardo, Michael Marcotte, Kayla Wong, Dishary Sharmin, Kamal Prakash Pandey, James M. Cook, Etienne Sibille, Thomas D. PrévotList of authors in order
- Landing page
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https://doi.org/10.1016/j.neurobiolaging.2024.12.001Publisher landing page
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YesWhether a free full text is available
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hybridOpen access status per OpenAlex
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https://doi.org/10.1016/j.neurobiolaging.2024.12.001Direct OA link when available
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Amyloid β, Neuroscience, Disease, Amyloid (mycology), Allosteric regulation, Neurotrophic factors, Pathology, Medicine, Biology, Receptor, Internal medicineTop concepts (fields/topics) attached by OpenAlex
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5Total citation count in OpenAlex
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2025: 4, 2024: 1Per-year citation counts (last 5 years)
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10Other works algorithmically related by OpenAlex
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| countries_distinct_count | 2 |
| institutions_distinct_count | 8 |
| citation_normalized_percentile.value | 0.89029471 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |