Hypoxic and Hypercapnic Responses in Transgenic Murine Model of Alzheimer's Disease Overexpressing Human AβPP: The Effects of Pretreatment with Memantine and Rivastigmine

Kryspin Andrzejewski, Monika Jampolska, Ilona Mojzych, Silvia V Conde, Katarzyna Kaczyńska

Research output: Contribution to journalArticlepeer-review

Abstract

Despite the severe respiratory problems reducing the quality of life for Alzheimer's disease (AD) patients, their causes are poorly understood. We aimed to investigate hypoxic and hypercapnic respiratory responses in a transgenic mouse model of AD (AβPP V717I) overexpressing AβPP 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-). 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 CO 2 sensitivity. Rivastigmine is a potent reductant of normoxic and hypercapnic respiration in APP+ and APP- mice.

Original languageEnglish
Article number6004
JournalInternational Journal of Molecular Sciences
Volume23
Issue number11
DOIs
Publication statusPublished - 26 May 2022

Keywords

  • Acetylcholinesterase
  • Alzheimer Disease/drug therapy
  • Animals
  • Disease Models, Animal
  • Humans
  • Hypercapnia/drug therapy
  • Hypoxia/drug therapy
  • Memantine/pharmacology
  • Mice
  • Mice, Transgenic
  • Quality of Life
  • Respiration
  • Rivastigmine/pharmacology

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