Deep brain stimulation of thalamic nucleus reuniens promotes neuronal and cognitive resilience in an Alzheimer's disease mouse model.
Nat Commun
; 14(1): 7002, 2023 11 02.
Article
em En
| MEDLINE
| ID: mdl-37919286
ABSTRACT
The mechanisms that confer cognitive resilience to Alzheimer's Disease (AD) are not fully understood. Here, we describe a neural circuit mechanism underlying this resilience in a familial AD mouse model. In the prodromal disease stage, interictal epileptiform spikes (IESs) emerge during anesthesia in the CA1 and mPFC regions, leading to working memory disruptions. These IESs are driven by inputs from the thalamic nucleus reuniens (nRE). Indeed, tonic deep brain stimulation of the nRE (tDBS-nRE) effectively suppresses IESs and restores firing rate homeostasis under anesthesia, preventing further impairments in nRE-CA1 synaptic facilitation and working memory. Notably, applying tDBS-nRE during the prodromal phase in young APP/PS1 mice mitigates age-dependent memory decline. The IES rate during anesthesia in young APP/PS1 mice correlates with later working memory impairments. These findings highlight the nRE as a central hub of functional resilience and underscore the clinical promise of DBS in conferring resilience to AD pathology by restoring circuit-level homeostasis.
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1
Base de dados:
MEDLINE
Assunto principal:
Estimulação Encefálica Profunda
/
Doença de Alzheimer
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article