Neural circuits expressing the serotonin 2C receptor regulate memory in mice and humans.
Sci Adv
; 10(26): eadl2675, 2024 Jun 28.
Article
em En
| MEDLINE
| ID: mdl-38941473
ABSTRACT
Declined memory is a hallmark of Alzheimer's disease (AD). Experiments in rodents and human postmortem studies suggest that serotonin (5-hydroxytryptamine, 5-HT) plays a role in memory, but the underlying mechanisms are unknown. Here, we investigate the role of 5-HT 2C receptor (5-HT2CR) in regulating memory. Transgenic mice expressing a humanized HTR2C mutation exhibit impaired plasticity of hippocampal ventral CA1 (vCA1) neurons and reduced memory. Further, 5-HT neurons project to and synapse onto vCA1 neurons. Disruption of 5-HT synthesis in vCA1-projecting neurons or deletion of 5-HT2CRs in the vCA1 impairs neural plasticity and memory. We show that a selective 5-HT2CR agonist, lorcaserin, improves synaptic plasticity and memory in an AD mouse model. Cumulatively, we demonstrate that hippocampal 5-HT2CR signaling regulates memory, which may inform the use of 5-HT2CR agonists in the treatment of dementia.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Camundongos Transgênicos
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Receptor 5-HT2C de Serotonina
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Doença de Alzheimer
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Memória
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Plasticidade Neuronal
Limite:
Animals
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Humans
Idioma:
En
Revista:
Sci Adv
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos