title: 5-HT1B and other related serotonergic proteins are altered in APPswe mutation.
abstract: Serotonergic dysfunction is implicated in Alzheimer's disease (AD). In addition, reductions in brain of both monoamine synthesis and release have been reported. Serotonin 1B receptors (5-HT1B), along with serotonin transporter (SERT) are among the regulators of extracellular 5-HT levels. We investigated the effect of the familial AD APP (Amyloid precursor protein) K670N/M671L double mutation, APP Swedish mutation (APPswe), on the expression of 5-HT1B, SERT, MAOA, p11 and 5-HT and its metabolite 5-HIAA in SH-SY5Y human neuroblastoma cell line stably transfected with APPswe mutation. In addition, hippocampal expressions of 5-HT1B and SERT were assessed in wild type and transgenic mice expressing APPswe mutation (Tg2576) at different age groups. We found a reduction of 5-HT1B as well as SERT in both APPswe in vitro and ex vivo. P11 and 5HT were also reduced, whereas 5HT turnover and MAOA were increased. Our results indicate that APPswe induced decreased 5-HT1B expression and 5-HT release, as well as increased MAOA activity and 5-HT breakdown. Further studies to explore the detailed mechanism behind reduced 5-HT1B and SERT in AD and their clinical implications are needed.
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Disease Research, Neurogeriatrics Division, Karolinska Institute, Novum, Blickagången 6, 141 57, Huddinge, Sweden.
authors.forename: Walid
authors.initials: W
authors.lastname: Tajeddinn
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Disease Research, Neurogeriatrics Division, Karolinska Institute, Novum, Blickagången 6, 141 57, Huddinge, Sweden.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Persson
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Disease Research, Neurogeriatrics Division, Karolinska Institute, Novum, Blickagången 6, 141 57, Huddinge, Sweden.
authors.forename: Silvia
authors.initials: S
authors.lastname: Maioli
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Disease Research, Neurogeriatrics Division, Karolinska Institute, Novum, Blickagången 6, 141 57, Huddinge, Sweden.
authors.forename: Javier
authors.initials: J
authors.lastname: Calvo-Garrido
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Disease Research, Neurogeriatrics Division, Karolinska Institute, Novum, Blickagången 6, 141 57, Huddinge, Sweden.
authors.forename: Cristina
authors.initials: C
authors.lastname: Parrado-Fernandez
authors.affiliation: Departments of Physiology and Pharmacology, Karolinska Institute, Solna, Sweden.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshitake
authors.affiliation: Departments of Physiology and Pharmacology, Karolinska Institute, Solna, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Kehr
authors.affiliation: King's College London, Wolfson Centre for Age Related-Diseases, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Francis
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Disease Research, Neurogeriatrics Division, Karolinska Institute, Novum, Blickagången 6, 141 57, Huddinge, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Disease Research, Neurogeriatrics Division, Karolinska Institute, Novum, Blickagången 6, 141 57, Huddinge, Sweden; Göteborg University Sahlgrenska Academy, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sweden.
authors.forename: Kina
authors.initials: K
authors.lastname: Höglund
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Disease Research, Neurogeriatrics Division, Karolinska Institute, Novum, Blickagången 6, 141 57, Huddinge, Sweden.
authors.forename: Angel
authors.initials: A
authors.lastname: Cedazo-Minguez
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Disease Research, Neurogeriatrics Division, Karolinska Institute, Novum, Blickagången 6, 141 57, Huddinge, Sweden; Centre for Age- Related Medicine, Stavanger University Hospital, Stavanger, Norway; Department of Neurology, Akershus University Hospital, Oslo, Norway. Electronic address: daarsland@gmail.com.
authors.forename: Dag
authors.initials: D
authors.lastname: Aarsland
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D017306:Annexin A2 / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008822:Mice, Transgenic; D008995:Monoamine Oxidase / Q000378:metabolism; D009154:Mutation; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D000099248:S100 Calcium Binding Protein A10
chemical_list: D016564:Amyloid beta-Protein Precursor; D017306:Annexin A2; D006897:Hydroxyindoleacetic Acid; D008995:Monoamine Oxidase; D044302:Receptor, Serotonin, 5-HT1B; D009418:S100 Proteins; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D000099248:S100 Calcium Binding Protein A10; C493230:SLC6A4 protein, human; C493231:Slc6a4 protein, mouse
keywords: 5-HT1B; APPswe; Alzheimer’s disease; SERT; Serotonin