Alterations of the sympathoadrenal axis related to the development of alzheimer’s disease in the 3xTg mouse model

Alzheimer’s disease (AD), the most common form of dementia, is becoming a global health problem and public health priority. In the advanced stages of AD, besides the initial cognitive symptoms, behavioral problems, particularly agitation and aggressiveness, become prevalent in AD patients. These non...

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Detalles Bibliográficos
Autores: Muñoz Montero, Alicia, de Pascual, Ricardo, Sáez-Mas, Anabel, Colmena, Inés, Gandía Juan, Luis
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/706600
Acceso en línea:http://hdl.handle.net/10486/706600
https://dx.doi.org/10.3390/biology11040511
Access Level:acceso abierto
Palabra clave:3xTg mouse model
Alzheimer’s disease
autocrine-paracrine modulation
chromaffin cell
sympathoadrenal axis
voltage-dependent calcium channels
Medicina
Descripción
Sumario:Alzheimer’s disease (AD), the most common form of dementia, is becoming a global health problem and public health priority. In the advanced stages of AD, besides the initial cognitive symptoms, behavioral problems, particularly agitation and aggressiveness, become prevalent in AD patients. These non-cognitive symptoms could be related to a noradrenergic overactivation. In this study, we used chromaffin cells (CCs) isolated from the adrenal gland of 3xTg AD model mice to characterize potential alterations in the autocrine-paracrine modulation of voltage-dependent calcium channels (VDCCs), which in turn serve to regulate the release of catecholamines. We used mice at the presymptomatic stage (2 months) and mice over 12 months of age, when AD-related cognitive impairment was fully established. We found that the modulation of inward currents through VDCCs induced by extracellular ATP was stronger in CCs isolated from the adrenal medulla of 3xTg mice older than 12 months of age, an effect likely related to disease progression as it was not observed in CCs from age-matched WT mice. This enhanced modulation leads to increased catecholamine release in response to stressful situations, which may explain the non-cognitive behavioral problems found in AD patients