{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:57:16Z","timestamp":1760151436925,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,26]],"date-time":"2022-03-26T00:00:00Z","timestamp":1648252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Econom\u00eda y Competitividad (MINECO)","award":["SAF2017-78892-R"],"award-info":[{"award-number":["SAF2017-78892-R"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Alzheimer\u2019s 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.<\/jats:p>","DOI":"10.3390\/biology11040511","type":"journal-article","created":{"date-parts":[[2022,3,27]],"date-time":"2022-03-27T21:27:51Z","timestamp":1648416471000},"page":"511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Alterations of the Sympathoadrenal Axis Related to the Development of Alzheimer\u2019s Disease in the 3xTg Mouse Model"],"prefix":"10.3390","volume":"11","author":[{"given":"Alicia","family":"Mu\u00f1oz-Montero","sequence":"first","affiliation":[{"name":"Instituto Te\u00f3filo Hernando and Departamento de Farmacolog\u00eda y Terap\u00e9utica, Universidad Aut\u00f3noma de Madrid, C\/ Arzobispo Morcillo, 4, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6628-6097","authenticated-orcid":false,"given":"Ricardo","family":"de Pascual","sequence":"additional","affiliation":[{"name":"Instituto Te\u00f3filo Hernando and Departamento de Farmacolog\u00eda y Terap\u00e9utica, Universidad Aut\u00f3noma de Madrid, C\/ Arzobispo Morcillo, 4, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9417-7418","authenticated-orcid":false,"given":"Anabel","family":"S\u00e1ez-Mas","sequence":"additional","affiliation":[{"name":"Instituto Te\u00f3filo Hernando and Departamento de Farmacolog\u00eda y Terap\u00e9utica, Universidad Aut\u00f3noma de Madrid, C\/ Arzobispo Morcillo, 4, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In\u00e9s","family":"Colmena","sequence":"additional","affiliation":[{"name":"Instituto Te\u00f3filo Hernando and Departamento de Farmacolog\u00eda y Terap\u00e9utica, Universidad Aut\u00f3noma de Madrid, C\/ Arzobispo Morcillo, 4, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9597-8519","authenticated-orcid":false,"given":"Luis","family":"Gand\u00eda","sequence":"additional","affiliation":[{"name":"Instituto Te\u00f3filo Hernando and Departamento de Farmacolog\u00eda y Terap\u00e9utica, Universidad Aut\u00f3noma de Madrid, C\/ Arzobispo Morcillo, 4, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The Amyloid Hypothesis of Alzheimer\u2019s Disease: Progress and Problems on the Road to Therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1126\/science.1074069","article-title":"Alzheimer\u2019s Disease Is a Synaptic Failure","volume":"298","author":"Selkoe","year":"2002","journal-title":"Science"},{"key":"ref_3","first-page":"1","article-title":"Revisiting the cholinergic hypothesis in alzheimer\u2019s disease: Emerging evidence from translational and clinical research","volume":"6","author":"Hampel","year":"2018","journal-title":"J. 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