Abstract：
:High-affinity transporters for norepinephrine (NE) and serotonin (5-HT), which ensure neurotransmitter clearance at the synapse, are the principal targets of widely used antidepressant drugs. Antidepressants targeting these high-affinity transporters, however, do not provide positive treatment outcomes for all patients. Other monoamine transport systems, with lower affinity, have been detected in the brain, but their role is largely unknown. Here we report that OCT2, a member of the polyspecific organic cation transporter (OCT) family, is expressed notably in the limbic system and implicated in anxiety and depression-related behaviors in the mouse. Genetic deletion of OCT2 in mice produced a significant reduction in brain tissue concentrations of NE and 5-HT and in ex vivo uptake of both these neurotransmitters in the presence of the dual 5-HT-NE transport blocker, venlafaxine. In vivo clearance of NE and 5-HT evaluated using microiontophoretic electrophysiology was diminished in the hippocampus of OCT2(-/-) mice in the presence of venlafaxine, thereby affecting postsynaptic neuronal activity. OCT2(-/-) mice displayed an altered sensitivity to acute treatments with NE- and/or 5-HT-selective transport blockers in the forced-swim test. Moreover, the mutant mice were insensitive to long-term venlafaxine treatment in a more realistic, corticosterone-induced, chronic depression model. Our findings identify OCT2 as an important postsynaptic determinant of aminergic tonus and mood-related behaviors and a potential pharmacological target for mood disorders therapy.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Bacq A,Balasse L,Biala G,Guiard B,Gardier AM,Schinkel A,Louis F,Vialou V,Martres MP,Chevarin C,Hamon M,Giros B,Gautron Sdoi
10.1038/mp.2011.87subject
Has Abstractpub_date
2012-09-01 00:00:00pages
926-39issue
9eissn
1359-4184issn
1476-5578pii
mp201187journal_volume
17pub_type
杂志文章abstract：:Serotonergic (5HT) neurons exert diverse and widespread functions in the brain. Dysfunction of the serotonergic system gives rise to a variety of mental illnesses including depression, anxiety, obsessive compulsive disorder, autism and eating disorders. Here we show that human primary fibroblasts were directly convert...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2015.101
更新日期：2016-01-01 00:00:00
abstract：:Cigarette smoking is more prevalent in subjects with schizophrenia compared to those with other psychiatric disorders or the general population and could therefore affect molecular pathways that impact the pathophysiology of this disorder. As smoking is also known to suppress immune responses, we investigated the effe...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2008.120
更新日期：2010-04-01 00:00:00
abstract：:Converging advances in the fields of molecular biology, molecular genetics, cellular biology and embryology have given researchers the tools for the targeted delivery and stable germline transmission of foreign genes (transgenes) in the mouse. In the realm of neuropsychiatry, this so-named transgenic technology has be...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：
更新日期：1996-05-01 00:00:00
abstract：:The literature on GWAS (genome-wide association studies) data suggests that very large sample sizes (for example, 50,000 cases and 50,000 controls) may be required to detect significant associations of genomic regions for complex disorders such as Alzheimer's disease (AD). Because of the challenges of obtaining such l...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2012.81
更新日期：2013-05-01 00:00:00
abstract：:Family studies have demonstrated genetic influences on environmental exposure: the phenomenon of gene-environment correlation (rGE). A few molecular genetic studies have confirmed the results, but the identification of rGE in studies that measure genes and environments faces several challenges. Using examples from stu...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/sj.mp.4001950
更新日期：2007-05-01 00:00:00
abstract：:Schizophrenia is a severe psychiatric disorder with a world-wide prevalence of 1%. The pathophysiology of the illness is not understood, but is thought to have a strong genetic component with some environmental influences on aetiology. To gain further insight into disease mechanism, we used microarray technology to de...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2009.18
更新日期：2009-12-01 00:00:00
abstract：:Endocannabinoids and their attending cannabinoid type 1 (CB1) receptor have been implicated in animal models of post-traumatic stress disorder (PTSD). However, their specific role has not been studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2013.61
更新日期：2013-09-01 00:00:00
abstract：:This study explores whether inflammatory biomarkers act as moderators of clinical response to omega-3 (n-3) fatty acids in subjects with major depressive disorder (MDD). One hundred fifty-five subjects with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) MDD, a baseline 17-item Hamilton Dep...
journal_title：Molecular psychiatry
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1038/mp.2015.22
更新日期：2016-01-01 00:00:00
abstract：:Corticotropin-releasing hormone (CRH) is the principal regulator of the hypothalamic-pituitary-adrenal (HPA) axis and an activator of the sympathoadrenal (SA) and systemic sympathetic (SS) systems. Mental disorders, including major depression and, more recently, Alzheimer's disease have been associated with dysregulat...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000720
更新日期：2000-03-01 00:00:00
abstract：:Many antidepressants stimulate adult hippocampal neurogenesis, but the mechanisms by which they increase neurogenesis and modulate behavior are incompletely understood. Here we show that hippocampal bone morphogenetic protein (BMP) signaling is modulated by antidepressant treatment, and that the changes in BMP signali...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2016.160
更新日期：2017-06-01 00:00:00
abstract：:Previous studies have implicated DTNBP1 as a schizophrenia susceptibility gene and its encoded protein, dysbindin, as a potential regulator of synaptic vesicle physiology. In this study, we found that endogenous levels of the dysbindin protein in the mouse brain are developmentally regulated, with higher levels observ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2009.58
更新日期：2010-02-01 00:00:00
abstract：:Abnormalities in prefrontal gamma aminobutyric acid (GABA)ergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders, including schizophrenia, bipolar disorder, anxiety disorders and depression. Wh...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2015.222
更新日期：2016-07-01 00:00:00
abstract：:Post-traumatic stress disorder (PTSD) is associated with elevated risk for a variety of age-related diseases and neurodegeneration. In this paper, we review evidence relevant to the hypothesis that chronic PTSD constitutes a form of persistent life stress that potentiates oxidative stress (OXS) and accelerates cellula...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/mp.2014.111
更新日期：2014-11-01 00:00:00
abstract：:The effect of endogenous dopamine (DA) on neostriatal DA D(1) and D(2) receptor binding potentials (D(1)RBP and D(2)RBP, respectively) in vivo was evaluated with positron emission tomography (PET) and the radiotracers [(11)C]SCH23390 and [(11)C]raclopride, respectively, by comparing the D(1)RBP and D(2)RBP before and ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001062
更新日期：2002-01-01 00:00:00
abstract：:Previous studies have shown inconsistent results regarding the actions of antidepressants on glucocorticoid receptor (GR) signalling. To resolve these inconsistencies, we used a lentiviral-based reporter system to directly monitor rat hippocampal GR activity during stress adaptation. Temporal GR activation was induced...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2014.137
更新日期：2016-02-01 00:00:00
abstract：:The hippocampus is critical to healthy cognition, yet results in the current study show that action video game players have reduced grey matter within the hippocampus. A subsequent randomised longitudinal training experiment demonstrated that first-person shooting games reduce grey matter within the hippocampus in par...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2017.155
更新日期：2018-07-01 00:00:00
abstract：:Circulating triglycerides (TGs) normally increase after a meal but are altered in pathophysiological conditions, such as obesity. Although TG metabolism in the brain remains poorly understood, several brain structures express enzymes that process TG-enriched particles, including mesolimbic structures. For this reason,...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2014.31
更新日期：2014-10-01 00:00:00
abstract：:TET3 is a member of the ten-eleven translocation (TET) family of enzymes which oxidize 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Tet3 is highly expressed in the brain, where 5hmC levels are most abundant. In adult mice, we observed that TET3 is present in mature neurons and oligodendrocytes but is ab...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-020-0695-7
更新日期：2020-02-26 00:00:00
abstract：:Bipolar disorder is a major medical, social and economic burden worldwide. However, the mechanisms of action of effective antibipolar disorder drugs remain elusive. In this paper, we review studies using a neuropharmacological approach in unanesthetized rats, combined with kinetic, biochemical and molecular biology te...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/mp.2008.31
更新日期：2008-06-01 00:00:00
abstract：:Among the different initiating events in Alzheimer's disease (AD) pathogenesis, oxidative stress and neuroinflammation are some of the most iimportant. In the central nervous system, the 12/15Lipoxygenase (12/15LO) enzyme is the source of potent pro-oxidants and inflammatory lipid mediators. Previous works showed that...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-018-0268-1
更新日期：2018-10-02 00:00:00
abstract：:Recent in vivo studies have shown low dopamine D2 receptor and dopamine transporter densities among late onset (type 1) alcoholics. We have now studied 6-[18F]-FDOPA (FDOPA) uptake in 10 type 1 alcoholics and eight matched controls to test the hypothesis that striatal presynaptic dopamine function is lower among alcoh...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000365
更新日期：1998-03-01 00:00:00
abstract：:Recent studies have revealed that the gut microbiota modulates brain development and behavior, but the underlying mechanisms are still poorly understood. Here, we show that bacterial peptidoglycan (PGN) derived from the commensal gut microbiota can be translocated into the brain and sensed by specific pattern-recognit...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2016.182
更新日期：2017-02-01 00:00:00
abstract：:Among the most consistent results of studies of post-mortem brain tissue from schizophrenia patients (SZP) is the finding that in this disease, several genes expressed by GABAergic neurons are downregulated. This downregulation may be caused by hypermethylation of the relevant promoters in affected neurons. Indeed, in...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001954
更新日期：2007-04-01 00:00:00
abstract：:The human serotonin transporter gene (5-HTT) demonstrates two polymorphisms with possible functional impact: a 44-bp insertion/deletion polymorphism of the promoter region and a 17-bp variable number of tandem repeat polymorphism (VNTR) in intron 2 (STin2). Such genetic polymorphisms in the serotoninergic system may i...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000821
更新日期：2001-03-01 00:00:00
abstract：:Major depressive disorder (MDD) is a common and severe disease characterized by mood changes, somatic alterations, and often suicide. MDD is treated with antidepressants, but the molecular mechanism of their action is unknown. We found that widely used antidepressants such as amitriptyline and fluoxetine induce autoph...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-018-0090-9
更新日期：2018-12-01 00:00:00
abstract：:This corrects the article DOI: 10.1038/mp.2017.5. ...
journal_title：Molecular psychiatry
pub_type： 杂志文章,已发布勘误
doi：10.1038/mp.2017.70
更新日期：2018-03-01 00:00:00
abstract：:Low hippocampal volume is a consistent finding in schizophrenia and across the psychosis spectrum. However, there is a lack of studies investigating longitudinal hippocampal development and its relationship with psychotic symptoms. The 22q11.2 deletion syndrome (22q11DS) has proven to be a remarkable model for the pro...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-019-0443-z
更新日期：2020-11-01 00:00:00
abstract：:Diverse studies have investigated the impact of prenatal exposure to vitamin D levels on brain development; however, evidence in humans has never been systematically reviewed. This article summarized evidence of the association between 25-hydroxyvitamin D [25(OH)D] levels in maternal blood in pregnancy or newborn bloo...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-019-0357-9
更新日期：2020-10-01 00:00:00
abstract：:Panic disorder (PD) has a lifetime prevalence of 2-4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide geno...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-019-0590-2
更新日期：2019-11-11 00:00:00
abstract：:Whilst cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers for amyloid-β (Aβ) and tau pathologies are accurate for the diagnosis of Alzheimer's disease (AD), their broad implementation in clinical and trial settings are restricted by high cost and limited accessibility. Plasma phosphorylated-ta...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-020-00923-z
更新日期：2020-10-26 00:00:00
