Early changes in Abeta levels in the brain of APPswe transgenic mice--implication on synaptic density, alpha7 neuronal nicotinic acetylcholine- and N-methyl-D-aspartate receptor levels.
Tg 2576 (APPswe) mice develop age-related amyloid deposition as well as behavioural- and electrophysiological changes in the brain. In this study, APPswe mice were investigated from 7 to 90 days of age. We observed high Abeta levels in the cortex of APPswe mice at 7 days of age, suggesting that these mice produce Abeta from birth. A positive correlation between Abeta and synaptophysin levels, followed by changes in ERK MAPK activity, indicated that Abeta causes altered synaptic function and an increase in the number of synaptic terminals. In addition, alterations in [(125)I]alphabungarotoxin- and [(3)H]MK-801 binding sites were also observed in APPswe mice compared to controls. In conclusion, over-expression of Abeta early in life causes changes in synaptophysin levels and number of [(125)I]alphabungarotoxin- and [(3)H]MK-801 binding sites. The results may provide important information about the onset and consequences of Abeta pathology in this transgenic mouse model.
Unger
Christina
C
Karolinska Institutet, Department of Neurotec, Division of Molecular Neuropharmacology, Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden.
Hedberg
Monika M
MM
Mustafiz
Tamanna
T
Svedberg
Marie M
MM
Nordberg
Agneta
A
D000375:Aging / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000502:physiology*; D002038:Bungarotoxins / Q000493:pharmacokinetics; D006224:Cricetinae; D016291:Dizocilpine Maleate / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D011328:Prions / Q000235:genetics; D011401:Promoter Regions, Genetic; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*
D016229:Amyloid beta-Peptides; D002038:Bungarotoxins; D011328:Prions; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D016291:Dizocilpine Maleate