Electrical stimulation of the medial forebrain bundle as a potential therapy for Alzheimer's disease: effects on molecular markers in rodent model

Electrical stimulation of deep brain areas has been suggested as a novel approach to restore memory circuits in Alzheimer’s disease (AD). Previous studies from our group have demonstrated that rewarding stimulation of the medial forebrain bundle (MFB-ICSS) facilitates learning and memory in healthy...

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Detalles Bibliográficos
Autor: Puig Parnau, Irene
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/672300
Acceso en línea:http://hdl.handle.net/10803/672300
Access Level:acceso abierto
Palabra clave:Malaltia d'Alzheimer
Enfermedad de Alzheimer
Alzheimer's disease
AD
Estimulació cerebral profunda
Estimulación cerebral profunda
Deep brain stimulation
DBS
Estimulació elèctrica
Estimulación eléctrica
Electrical stimulation
Autoestimulació intracranial
Autoestimulación intracraneal
Intracranial self-stimulation
ICSS
Feix prosencefàlic medial
Haz prosencefálico medial
Medial forebrain bundle
MFB
Marcadors moleculars
Marcadores moleculares
Molecular markers
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Descripción
Sumario:Electrical stimulation of deep brain areas has been suggested as a novel approach to restore memory circuits in Alzheimer’s disease (AD). Previous studies from our group have demonstrated that rewarding stimulation of the medial forebrain bundle (MFB-ICSS) facilitates learning and memory in healthy and brain-lesioned rats. This thesis assesses for the first time the effect of MFB-ICSS on AD-associated molecules and its relation with cognitive outcome in rats, including amyloid-β and streptozotocin sporadic AD models. Results confirmed that MFB-ICSS modulates AD-related molecules and facilitates memory in this condition. Specifically, amyloid precursor protein (APP), phosphorylated tau and key gene expression regulators like SIRT1 and particular microRNAs are modulated by MFB-ICSS in the hippocampus of treated rats. Moreover, effects on miR-132 and SIRT1 were also observed in blood, suggesting a potential use of these molecules as non-invasive biomarkers. Altogether, these data sustain the MFB as a promising stimulation target for AD treatment.