title: Serotonin 6 receptor controls Alzheimer's disease and depression.
abstract: Alzheimer's disease (AD) and depression in late life are one of the most severe health problems in the world disorders. Serotonin 6 receptor (5-HT6R) has caused much interest for potential roles in AD and depression. However, a causative role of perturbed 5-HT6R function between two diseases was poorly defined. In the present study, we found that a 5-HT6R antagonist, SB271036 rescued memory impairment by attenuating the generation of Aβ via the inhibition of γ-secretase activity and the inactivation of astrocytes and microglia in the AD mouse model. It was found that the reduction of serotonin level was significantly recovered by SB271036, which was mediated by an indirect regulation of serotonergic neurons via GABA. Selective serotonin reuptake inhibitor (SSRI), fluoxetine significantly improved cognitive impairment and behavioral changes. In human brain of depression patients, we then identified the potential genes, amyloid beta (A4) precursor protein-binding, family A, member 2 (APBA2), well known AD modulators by integrating datasets from neuropathology, microarray, and RNA seq. studies with correlation analysis tools. And also, it was demonstrated in mouse models and patients of AD. These data indicate functional network of 5-HT6R between AD and depression.
authors.affiliation: Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Hyung-Mun
authors.initials: HM
authors.lastname: Yun
authors.affiliation: Department of Oral & Maxillofacial Regeneration, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Kyung-Ran
authors.initials: KR
authors.lastname: Park
authors.affiliation: Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
authors.affiliation: Stanley Brain Research Laboratory, Stanley Medical Research Institute, Rockville, MD, USA.
authors.forename: Sanghyeon
authors.initials: S
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Republic of Korea.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D000682:Amyloid / Q000737:chemistry; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003072:Cognition Disorders / Q000378:metabolism; D003863:Depression / Q000175:diagnosis / Q000235:genetics*; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000737:chemistry; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000188:drug therapy; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments / Q000737:chemistry*; D011985:Receptors, Serotonin / Q000235:genetics* / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D059326:Serotonergic Neurons; D012702:Serotonin Antagonists / Q000737:chemistry*; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000737:chemistry
chemical_list: C079091:APBA1 protein, human; C491636:APBA2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000682:Amyloid; D016229:Amyloid beta-Peptides; C513072:Apba1 protein, mouse; C491635:Apba2 protein, mouse; D015820:Cadherins; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; C075222:amyloid beta-protein (1-42); C097216:serotonin 6 receptor; D005473:Fluoxetine; D053829:Amyloid Precursor Protein Secretases
keywords: 5-HT6R; APBA1/2; Alzheimer’s disease; depression; serotonin