Evaluation der Minimalen Alveolären Konzentration von Isofluran bei zwei transgenen Mausmodellen für die Alzheimer Krankheit

Abstract

According to studies an estimated 5 per cent of people older than 65 years are suffering from Alzheimer’s disease. The pathology of this disease might also influence some anaesthesiological parameters. The aim of this study is to investigate the effect of the Alzheimer- like pathology on the minimal alveolar concentration (MAC) of isoflurane in two mice models of Alzheimer’s disease. The MAC values of isoflurane were determined in twelve fifty month old, transgenic APP23 male mice, which over-express a human amyloid precursor protein with the Swedish double mutation and of twelve of their non-transgenic littermates. In the same way, the MAC values of twelve fifty month old, male transgenic APP51 mice, which carry the same genetic construct as the APP23, however, without the Swedish double mutation and of twelve of their non-transgenic littermates were determined. The animals breathed isoflurane in oxygen/air (FiO2=0,5) spontaneously through a nose chamber. The motor reaction to toe-clamping was recorded at various end-expiratory measured concentrations of isoflurane. An individual MAC was defined as the average between the largest isoflurane concentration permitting movement and the smallest concentration preventing it. The average of this individual MAC values was taken as the MAC of a test group. Statistical analysis was made with an unpaired t-test (p<0,05). The APP23 mice had significantly greater MAC values than their non-transgenic littermates. The MAC value of the APP51 was significantly lower than those of their non-transgenic group compared to. These results strongly pointed out that the higher MAC values of the APP23 mice are due to the effect of the Swedish double mutation and are not only a consequence of the overexpression of the human amyloid precursor protein or the genetic construct. Several Alzheimer typical alterations like neurotransmitter imbalances may be considered as explanations for the result of the APP23 mice. Further studies are needed to clarify this in detail.

• Item Type: Thesis (Dissertation, LMU Munich)
• Keywords: Alzheimer, Mausmodelle, MAC-Wert, Isofluran
• Dewey Decimal Classification: 600 Natural sciences and mathematics; 600 Natural sciences and mathematics > 590 Zoological sciences
• Faculties: Faculty of Veterinary Medicine
• Language: German
• Date Accepted: 09. February 2007
• 1. Referee: Erhard, Michael
• Persistent Identifier (URN): urn:nbn:de:bvb:19-65193
• Signature of the printed copy: 0001/UMC 15977