5-HT1B and other related serotonergic proteins are altered in APPswe mutation

• Published in: Neuroscience letters Vol. 594; pp. 137 - 143
• Main Authors: Tajeddinn, Walid, Persson, Torbjörn, Maioli, Silvia, Calvo-Garrido, Javier, Parrado-Fernandez, Cristina, Yoshitake, Takashi, Kehr, Jan, Francis, Paul, Winblad, Bengt, Höglund, Kina, Cedazo-Minguez, Angel, Aarsland, Dag
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 06-05-2015
• Subjects: 5-HT1B; Alzheimer Disease - metabolism; Alzheimer's disease; ALZHEIMERS-DISEASE; Amyloid beta-Protein Precursor - genetics; Animals; Annexin A2 - metabolism; APPswe; AWAKE RATS; Cell Line, Tumor; Clinical Medicine; DEPRESSION; DYSFUNCTION; Female; Hippocampus - metabolism; Humans; Hydroxyindoleacetic Acid - metabolism; INCREASES; Klinisk medicin; Medicin och hälsovetenskap; Mice, Transgenic; Monoamine Oxidase - metabolism; Mutation; PATHOLOGY; POSTMORTEM; PREFRONTAL CORTEX; Receptor, Serotonin, 5-HT1B - genetics; Receptor, Serotonin, 5-HT1B - metabolism; RECEPTORS; S100 Proteins - metabolism; Serotonin; Serotonin - metabolism; Serotonin Plasma Membrane Transport Proteins - metabolism; SERT; SYMPTOMS; AD; PS; Serotonin; Alzheimer’s disease; IHC; SLC6A4; Tg2576; SERT; ANOVA; APPswe; 5-HT1B; 5-HT; GAPDH; WT; PET
• ISSN: 0304-3940; 1872-7972; 1872-7972
• DOI: 10.1016/j.neulet.2015.03.064

•Both in vitro and ex vivo models with APPswe mutation are used.•5-HT1B and SERT expressions are reduced in APPswe models.•Previous report of reduced released 5-HT in AD models is confirmed.
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.