title: Aβ-42 deposition significantly increases the insolubility of synaptophysin in the brains of hAPPsw/hPS2m double transgenic mice.
abstract: Synaptophysin is a synaptic vesicle glycoprotein involved in the regulation process for neurotransmitter release, which is distributed throughout neuroendocrine cells and all neurons in the brain and spinal cord. In an effort to determine whether amyloid β (Aβ)-42 peptides could influence the quantity and biochemical properties of synaptophysin, alterations in the levels of the synaptophysin protein in various soluble fractions were detected in the brains of four genotypes of transgenic mice (Tg) including Non-Tg, neuron-specific enolase (NSE)-hPS2m, NSE-hAPPsw and hAPPsw/hPS2m double Tg mice. Among the four genotypes of Tg mice, the highest levels of Aβ-42 peptides were noted in hAPPsw/hPS2m, followed by NSE-hAPPsw, NSE-hPS2m and Non-Tg mice. In the brains of these mice displaying different levels of Aβ-42 peptides, the levels of soluble synaptophysin were reduced significantly only in the hAPPsw/hPS2m double Tg mice compared to the Non-Tg mice. However, immunohistochemical analysis revealed no differences in the levels of total synaptophysin protein between the neocortex and hippocampus of the four different genotypes of mice. Western blot analysis using four-step fractions with differing solubility revealed a marked decrease in synaptophysin levels in the Tris-buffer saline fraction of hAPPsw/hPS2m double Tg mice and a significant increase in the formic acid fraction, relative to the Non-Tg mice. The results obtained from our in vivo experiments in mice are identical to the results observed in SK-N-MC cells treated with 100 nM Aβ-42 peptides. Therefore, our experiments collectively suggest that Aβ-42 peptides may alter the solubility without changing the total amount of synaptophysin.
authors.affiliation: Department of Biomaterials Science, College of Natural Resources and Life Science, Pusan National University, Miryang 627-706, Republic of Korea.
authors.forename: Dae Youn
authors.initials: DY
authors.lastname: Hwang
authors.forename: Seung Wan
authors.initials: SW
authors.lastname: Jee
authors.forename: Su Hae
authors.initials: SH
authors.lastname: Lee
authors.forename: Chang Jun
authors.initials: CJ
authors.lastname: Bae
authors.forename: Jun Seo
authors.initials: JS
authors.lastname: Goo
authors.forename: Jee Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: So Hee
authors.initials: SH
authors.lastname: Nam
authors.forename: Sun Il
authors.initials: SI
authors.lastname: Choi
authors.forename: Hye Ryun
authors.initials: HR
authors.lastname: Lee
authors.forename: Sun Bo
authors.initials: SB
authors.lastname: Shim
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Park
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Hye Sung
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism; D012995:Solubility; D016708:Synaptophysin / Q000378:metabolism*
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D016708:Synaptophysin