title: Localization and expression of substance P in transgenic mice overexpressing human APP751 with the London (V717I) and Swedish (K670M/N671L) mutations.
abstract: Substance P-like immunoreactivity (-LI) is found in neuritic plaques, and is reduced in patients suffering from Alzheimer disease (AD). In this study, we examined the distribution and expression of substance P in transgenic mice overexpressing human amyloid precursor protein (hAPP) APP751 with the London (V717I) and Swedish (K670M/N671L) mutations. Immunohistochemistry was performed to localize substance P- and glial fibrillary acidic protein-LI by confocal microscopy. In hAPP transgenic mice, the number of beta-amyloid plaques significantly increased from 6 to 12 months. About 5% of beta-amyloid plaques were substance P-immunoreactive. In transgenic mice, the morphology of substance P-immunoreactive structures changed by consisting of swollen and dystrophic neurites mostly associated with beta-amyloid plaques. The overall localization and the relative substance P densities were not different between wild type and transgenic mice at 6 and 12 months. At month 12, a dramatic change in the distribution pattern of substance P-LI was observed as it was now expressed in a high number of reactive astrocytes. This expression of substance P in astrocytes was mainly found in the hippocampal formation and thalamic nuclei with a preferential association with beta-amyloid plaques, whereas in cortical regions only faintly substance P-immunoreactive astrocytes were observed. This study indicates that substance P undergoes complex changes in this animal Alzheimer disease model. Future experiments including substance P antagonists are necessary to further explore the interaction between beta-amyloid deposits and substance P.
authors.affiliation: Department of General Psychiatry, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Willis
authors.forename: Birgit
authors.initials: B
authors.lastname: Hutter-Paier
authors.forename: Georg
authors.initials: G
authors.lastname: Wietzorrek
authors.forename: Manfred
authors.initials: M
authors.lastname: Windisch
authors.forename: Christian
authors.initials: C
authors.lastname: Humpel
authors.forename: Hans Günther
authors.initials: HG
authors.lastname: Knaus
authors.forename: Josef
authors.initials: J
authors.lastname: Marksteiner
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000235:genetics; D015870:Gene Expression / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D007930:Leucine / Q000235:genetics; D008239:Lysine / Q000235:genetics; D008715:Methionine / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D013373:Substance P / Q000235:genetics / Q000378:metabolism*; D014633:Valine / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein; D007532:Isoleucine; D001224:Aspartic Acid; D013373:Substance P; D008715:Methionine; D007930:Leucine; D014633:Valine; D008239:Lysine