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Serotonin 6 receptor controls Alzheimer's disease and depression.
- Source :
-
Oncotarget [Oncotarget] 2015 Sep 29; Vol. 6 (29), pp. 26716-28. - Publication Year :
- 2015
-
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.
- Subjects :
- Adaptor Proteins, Signal Transducing metabolism
Alzheimer Disease diagnosis
Alzheimer Disease drug therapy
Amyloid chemistry
Amyloid Precursor Protein Secretases metabolism
Animals
Astrocytes cytology
Astrocytes metabolism
Behavior, Animal
Brain drug effects
Brain pathology
Cadherins metabolism
Carrier Proteins metabolism
Cognition Disorders metabolism
Depression diagnosis
Disease Models, Animal
Fluoxetine chemistry
Humans
Inflammation
Male
Maze Learning
Memory Disorders drug therapy
Mice
Mice, Inbred ICR
Microglia metabolism
Nerve Tissue Proteins metabolism
Oligonucleotide Array Sequence Analysis
Sequence Analysis, RNA
Serotonergic Neurons
Serotonin and Noradrenaline Reuptake Inhibitors chemistry
Alzheimer Disease genetics
Amyloid beta-Peptides chemistry
Depression genetics
Gene Expression Regulation
Peptide Fragments chemistry
Receptors, Serotonin genetics
Receptors, Serotonin metabolism
Serotonin Antagonists chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 6
- Issue :
- 29
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 26449188
- Full Text :
- https://doi.org/10.18632/oncotarget.5777