Localization and expression of substance P in transgenic mice overexpressing human APP751 with the London (V717I) and Swedish (K670M/N671L) mutations

• Published in: Brain research 2007-04, Vol.1143, p.199-207
• Main Authors: Willis, Michael, Hutter-Paier, Birgit, Wietzorrek, Georg, Windisch, Manfred, Humpel, Christian, Knaus, Hans Günther, Marksteiner, Josef
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Alzheimer; Amyloid; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Animals; APP; Aspartic Acid - genetics; Astrocyte; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Gene Expression - genetics; GFAP; Glial Fibrillary Acidic Protein - metabolism; Humans; Isoleucine - genetics; Leucine - genetics; Lysine - genetics; Medical sciences; Methionine - genetics; Mice; Mice, Transgenic; Mutation; Neurology; Organic mental disorders. Neuropsychology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Substance P; Substance P - genetics; Substance P - metabolism; Transgenic animal; Valine - genetics
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2007.01.080

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 β-amyloid plaques significantly increased from 6 to 12 months. About 5% of β-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 β-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 β-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 β-amyloid deposits and substance P.