Cholecystokinin B receptor agonists alleviates anterograde amnesia in cholecystokinin-deficient and aged Alzheimer's disease mice.
Animals
Alzheimer Disease
/ drug therapy
Mice
Receptor, Cholecystokinin B
/ genetics
Amnesia, Anterograde
/ drug therapy
Cholecystokinin
/ metabolism
Mice, Transgenic
Disease Models, Animal
Entorhinal Cortex
/ drug effects
Male
Mice, Knockout
Mice, Inbred C57BL
Long-Term Potentiation
/ drug effects
Hippocampus
/ metabolism
Aging
/ drug effects
Alzheimer’s disease
Anterograde amnesia
Cholecystokinin
Cholecystokinin B receptor agonist
HT-267
Journal
Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643
Informations de publication
Date de publication:
15 May 2024
15 May 2024
Historique:
received:
06
09
2023
accepted:
01
05
2024
medline:
16
5
2024
pubmed:
16
5
2024
entrez:
15
5
2024
Statut:
epublish
Résumé
As one major symptom of Alzheimer's disease (AD), anterograde amnesia describes patients with an inability in new memory formation. The crucial role of the entorhinal cortex in forming new memories has been well established, and the neuropeptide cholecystokinin (CCK) is reported to be released from the entorhinal cortex to enable neocortical associated memory and long-term potentiation. Though several studies reveal that the entorhinal cortex and CCK are related to AD, it is less well studied. It is unclear whether CCK is a good biomarker or further a great drug candidate for AD. mRNA expressions of CCK and CCK-B receptor (CCKBR) were examined in two mouse models, 3xTg AD and CCK knock-out (CCK Aged 3xTg AD mice exhibited reduced CCK mRNA expression in the entorhinal cortex but reduced CCKBR expression in the neocortex and hippocampus, and impaired cognition and neuroplasticity comparable with CCK Here we provide more evidence to support the role of CCK in learning and memory and its potential to treat AD. We elaborated on the rescue effect of a promising novel drug, HT-267, on aged 3xTg AD mice. Although the physiological etiology of CCK in AD still needs to be further investigated, this study sheds light on a potential pharmaceutical candidate for AD and dementia.
Sections du résumé
BACKGROUND
BACKGROUND
As one major symptom of Alzheimer's disease (AD), anterograde amnesia describes patients with an inability in new memory formation. The crucial role of the entorhinal cortex in forming new memories has been well established, and the neuropeptide cholecystokinin (CCK) is reported to be released from the entorhinal cortex to enable neocortical associated memory and long-term potentiation. Though several studies reveal that the entorhinal cortex and CCK are related to AD, it is less well studied. It is unclear whether CCK is a good biomarker or further a great drug candidate for AD.
METHODS
METHODS
mRNA expressions of CCK and CCK-B receptor (CCKBR) were examined in two mouse models, 3xTg AD and CCK knock-out (CCK
RESULTS
RESULTS
Aged 3xTg AD mice exhibited reduced CCK mRNA expression in the entorhinal cortex but reduced CCKBR expression in the neocortex and hippocampus, and impaired cognition and neuroplasticity comparable with CCK
CONCLUSIONS
CONCLUSIONS
Here we provide more evidence to support the role of CCK in learning and memory and its potential to treat AD. We elaborated on the rescue effect of a promising novel drug, HT-267, on aged 3xTg AD mice. Although the physiological etiology of CCK in AD still needs to be further investigated, this study sheds light on a potential pharmaceutical candidate for AD and dementia.
Identifiants
pubmed: 38750512
doi: 10.1186/s13195-024-01472-1
pii: 10.1186/s13195-024-01472-1
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
109Subventions
Organisme : Hong Kong Research Grants Council, General Research Fund
ID : 11103220, 11103922, 11101818
Organisme : Hong Kong Research Grants Council, Collaborative Research Fund
ID : C1043-21G
Organisme : Hong Kong Research Grants Council, Theme-Based Research Scheme
ID : T13-605/18-W
Organisme : Innovation and Technology Fund
ID : GHP_075_19GD
Organisme : Health and Medical Research Fund
ID : 08194106, 09203656
Informations de copyright
© 2024. The Author(s).
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