Chronic Neuronal Hyperexcitation Exacerbates Tau Propagation in a Mouse Model of Tauopathy.
Int J Mol Sci
; 25(16)2024 Aug 19.
Article
em En
| MEDLINE
| ID: mdl-39201689
ABSTRACT
The intracerebral spread of tau is a critical mechanism associated with functional decline in Alzheimer's disease (AD) and other tauopathies. Recently, a hypothesis has emerged suggesting that tau propagation is linked to functional neuronal connections, specifically driven by neuronal hyperactivity. However, experimental validation of this hypothesis remains limited. In this study, we investigated how tau propagation from the entorhinal cortex to the hippocampus, the neuronal circuit most susceptible to tau pathology in AD, is affected by the selective stimulation of neuronal activity along this circuit. Using a mouse model of seed-induced propagation combined with optogenetics, we found that the chronic stimulation of this neuronal connection over a 4-week period resulted in a significant increase in insoluble tau accumulation in both the entorhinal cortex and hippocampus. Importantly, the ratio of tau accumulation in the hippocampus relative to that in the entorhinal cortex, serving as an indicator of transcellular spreading, was significantly higher in mice subjected to chronic stimulation. These results support the notion that abnormal neuronal activity promotes tau propagation, thereby implicating it in the progression of tauopathy.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas tau
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Córtex Entorrinal
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Tauopatias
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Modelos Animais de Doenças
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Hipocampo
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Japão
País de publicação:
Suíça