{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T08:39:51Z","timestamp":1788683991520,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite the severe respiratory problems reducing the quality of life for Alzheimer\u2019s disease (AD) patients, their causes are poorly understood. We aimed to investigate hypoxic and hypercapnic respiratory responses in a transgenic mouse model of AD (A\u03b2PP V717I) overexpressing A\u03b2PP and mimicking early-onset AD. The cholinesterase inhibitor rivastigmine and the NMDA receptor antagonist memantine were used to investigate the effects of drugs, used to treat AD cognitive dysfunction, on breathing in hypoxia and hypercapnia. We found a significant increase in the respiratory response to hypercapnia and no difference in the hypoxic response in APP+ mice, compared with the control group (APP\u2212). Memantine had no effect on respiration in either group, including responses to hypoxia and hypercapnia. Rivastigmine depressed resting ventilation and response to hypercapnia irrespective of the mice genotype. Reduction in hypoxia-augmented ventilation by rivastigmine was observed only in APP+ mice, which exhibited lower acetylcholinesterase activity in the hippocampus. Treatment with rivastigmine reduced the enzyme activity in both groups equally in the hippocampus and brainstem. The increased ventilatory response to hypercapnia in transgenic mice may indicate alterations in chemoreceptive respiratory nuclei, resulting in increased CO2 sensitivity. Rivastigmine is a potent reductant of normoxic and hypercapnic respiration in APP+ and APP\u2212 mice.<\/jats:p>","DOI":"10.3390\/ijms23116004","type":"journal-article","created":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T07:05:07Z","timestamp":1653635107000},"page":"6004","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hypoxic and Hypercapnic Responses in Transgenic Murine Model of Alzheimer\u2019s Disease Overexpressing Human A\u03b2PP: The Effects of Pretreatment with Memantine and Rivastigmine"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-2813","authenticated-orcid":false,"given":"Kryspin","family":"Andrzejewski","sequence":"first","affiliation":[{"name":"Department of Respiration Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawi\u0144skiego 5 St., 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Jampolska","sequence":"additional","affiliation":[{"name":"Department of Respiration Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawi\u0144skiego 5 St., 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilona","family":"Mojzych","sequence":"additional","affiliation":[{"name":"Department of Respiration Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawi\u0144skiego 5 St., 02-106 Warsaw, Poland"},{"name":"Department of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5920-5700","authenticated-orcid":false,"given":"Silvia V.","family":"Conde","sequence":"additional","affiliation":[{"name":"Faculdade de Ciencias M\u00e9dicas, NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9608-4736","authenticated-orcid":false,"given":"Katarzyna","family":"Kaczy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Respiration Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawi\u0144skiego 5 St., 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"b158","DOI":"10.1136\/bmj.b158","article-title":"Alzheimer\u2019s disease","volume":"338","author":"Burns","year":"2009","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1037\/a0029857","article-title":"The natural history of cognitive decline in Alzheimer\u2019s disease","volume":"27","author":"Wilson","year":"2012","journal-title":"Psychol. 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