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 converted to induced serotonergic (i5HT) neurons by the expression of Ascl1, Foxa2, Lmx1b and FEV. The transdifferentiation was enhanced by p53 knockdown and appropriate culture conditions including hypoxia. The i5HT neurons expressed markers for mature serotonergic neurons, had Ca(2+)-dependent 5HT release and selective 5HT uptake, exhibited spontaneous action potentials and spontaneous excitatory postsynaptic currents. Application of serotonin significantly increased the firing rate of spontaneous action potentials, demonstrating the functional utility of i5HT neurons for studying serotonergic neurotransmission. The availability of human i5HT neurons will be very useful for research and drug discovery on many serotonin-related mental disorders.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Xu Z,Jiang H,Zhong P,Yan Z,Chen S,Feng Jdoi
10.1038/mp.2015.101subject
Has Abstractpub_date
2016-01-01 00:00:00pages
62-70issue
1eissn
1359-4184issn
1476-5578pii
mp2015101journal_volume
21pub_type
杂志文章abstract::Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, and limitations identifying those at risk. Prior studies suggest that PTSD may be a systemic illness, affecting not ju...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0496-z
更新日期:2020-12-01 00:00:00
abstract::Medical treatment with various cytokines can provoke psychiatric symptoms. Conversely, psychiatric patients can display abnormalities in cytokine and neurotrophic factor expression. Such observations have pointed to the potential contribution of cytokines and growth factors to schizophrenic pathology and/or etiology. ...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/sj.mp.4000730
更新日期:2000-11-01 00:00:00
abstract::Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) rev...
journal_title:Molecular psychiatry
pub_type: 杂志文章,meta分析
doi:10.1038/mp.2016.231
更新日期:2018-02-01 00:00:00
abstract::A polymorphism in the serotonin (5-HT) transporter gene regulatory region (5-HTTLPR) is associated with measures of 5-HT transporter (5-HTT) expression and 5-HT-mediated behaviors in humans. An analogous length variation of the 5-HTTLPR has been reported in rhesus monkeys (rh5-HTTLPR). A retrospective association stud...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001157
更新日期:2002-01-01 00:00:00
abstract::Depression often accompanies the perimenopausal transition and it often precedes overt symptomology in common neurodegenerative diseases (NDDs, such as Alzheimer's, Parkinson's, Huntington, amyotrophic lateral sclerosis). Serotonin dysfunction is frequently found in the different etiologies of depression. We have show...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2014.178
更新日期:2015-12-01 00:00:00
abstract::The 102-T/C polymorphism of the 5-HT(2A) receptor gene was analysed in 159 patients with major depression and 164 unrelated and healthy controls using a case-control design. Allele and genotype frequencies did not differ between cases and controls. No differences according to sex, age of onset, melancholia, suicidal b...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000818
更新日期:2001-03-01 00:00:00
abstract::Exposure to severe stressors increases the risk for psychiatric disorders in vulnerable individuals, but can lead to positive outcomes for others. However, it remains unknown how severe stress affects neural functioning in humans and what factors mediate individual differences in the neural sequelae of stress. The amy...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2010.132
更新日期:2011-06-01 00:00:00
abstract::A whole genome association study was performed in a phase 3 clinical trial conducted to evaluate a novel antipsychotic, iloperidone, administered to treat patients with schizophrenia. Genotypes of 407 patients were analyzed for 334,563 single nucleotide polymorphisms (SNPs). SNPs associated with iloperidone efficacy w...
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.2008.56
更新日期:2009-08-01 00:00:00
abstract::Autism spectrum disorder (ASD) is characterized by neurocognitive dysfunctions, such as impaired social interaction and language learning. Gene-environment interactions have a pivotal role in ASD pathogenesis. Nuclear receptor corepressors (NCORs) are transcription co-regulators physically associated with histone deac...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/s41380-020-0667-y
更新日期:2020-10-01 00:00:00
abstract::Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelop...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2012.161
更新日期:2014-01-01 00:00:00
abstract::Negative affect (NA) is a significant cause of disability for chronic pain patients. While little is known about the mechanism underlying pain-comorbid NA, previous studies have implicated neuroinflammation in the pathophysiology of both depression and chronic pain. Here, we tested the hypothesis that NA in pain patie...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0433-1
更新日期:2019-05-28 00:00:00
abstract::We assessed the ability of lithium to reduce neurodegeneration and to stimulate cell proliferation in a rat model of Huntington's disease in which quinolinic acid (QA) was unilaterally infused into the striatum. LiCl (0.5-3.0 mEq/kg) was injected subcutaneously 24 h before and 1 h after QA infusion. At 7 days after QA...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001463
更新日期:2004-04-01 00:00:00
abstract::Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and families have identifi...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0087-4
更新日期:2018-12-01 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::Serotonin (5-HT) neurons project from the raphe nuclei throughout the brain where they act to maintain homeostasis. Here, we study 5-HT inputs into the bed nucleus of the stria terminalis (BNST), a major subdivision of the extended amygdala that has been proposed to regulate responses to anxiogenic environments in hum...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.165
更新日期:2018-10-01 00:00:00
abstract::Traumatic life experiences are associated with alcohol use problems, an association that is likely to be moderated by genetic predisposition. To understand these interactions, we conducted a gene-by-environment genome-wide interaction study (GEWIS) of alcohol use problems in two independent samples, the Army STARRS (S...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.24
更新日期:2018-01-01 00:00:00
abstract::Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations betwee...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-00976-0
更新日期:2021-01-07 00:00:00
abstract::Identifying genes for bipolar mood disorders through classic genetics has proven difficult. Here, we present a comprehensive convergent approach that translationally integrates brain gene expression data from a relevant pharmacogenomic mouse model (involving treatments with a stimulant--methamphetamine, and a mood sta...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001547
更新日期:2004-11-01 00:00:00
abstract::Disruption of persistent, stress-associated memories is relevant for treating posttraumatic stress disorder (PTSD) and related syndromes, which develop in a subset of individuals following a traumatic event. We previously developed a stress-enhanced fear learning (SEFL) paradigm in inbred mice that produces PTSD-like ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0432-2
更新日期:2020-05-01 00:00:00
abstract::Autism spectrum disorder (ASD) and schizophrenia (SCZ) are two common neurodevelopmental syndromes that result from the combined effects of environmental and genetic factors. We set out to test the hypothesis that rare variants in many different genes, including de novo variants, could predispose to these conditions i...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2010.54
更新日期:2011-08-01 00:00:00
abstract::Polymorphism in the human dopamine D4 receptor gene (DRD4) exon III has been associated in some but not all studies of the human personality trait of Novelty Seeking. We searched for polymorphisms in the 5' region of DRD4 and identified six polymorphisms as follows: -1217G Ins/Del, -809G/A, -616C/G, -603T Ins/Del, -60...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000563
更新日期:2000-01-01 00:00:00
abstract::Bipolar disorder (BPD) is characterized by vulnerability to episodic depression and mania and spontaneous cycling. Because of marked advances in candidate-gene and genome-wide association studies, the list of risk genes for BPD is growing rapidly, creating an unprecedented opportunity to understand the pathophysiology...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/mp.2010.3
更新日期:2010-09-01 00:00:00
abstract::Here, we report a novel target of the drug memantine, ATP-sensitive K+ (KATP) channels, potentially relevant to memory improvement. We confirmed that memantine antagonizes memory impairment in Alzheimer's model APP23 mice. Memantine increased CaMKII activity in the APP23 mouse hippocampus, and memantine-induced enhanc...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2016.187
更新日期:2018-02-01 00:00:00
abstract::The methionine-folate cycle-dependent one-carbon metabolism is implicated in the pathophysiology of schizophrenia. Since schizophrenia is a developmental disorder, we examined the effects that perturbation of the one-carbon metabolism during gestation has on mice progeny. Pregnant mice were administered methionine equ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.164
更新日期:2018-02-01 00:00:00
abstract::Chronic stress contributes to the development of psychiatric disorders including anxiety and depression. Several inflammatory-related effects of stress are associated with increased interleukin-1 (IL-1) signaling within the central nervous system and are mediated by IL-1 receptor 1 (IL-1R1) on several distinct cell ty...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-0788-3
更新日期:2020-05-22 00:00:00
abstract::Human neural progenitors from a variety of sources present new opportunities to model aspects of human neuropsychiatric disease in vitro. Such in vitro models provide the advantages of a human genetic background combined with rapid and easy manipulation, making them highly useful adjuncts to animal models. Here, we ex...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2011.60
更新日期:2012-02-01 00:00:00
abstract::Recent studies report association and linkage between attention deficit hyperactivity disorder (ADHD) and the 7-repeat allele of a 48 base-pair repeat in the dopamine D4 receptor gene (DRD4). We examined the frequency of this allele in a sample of probands with DSM-IV ADHD using a case-control design, as well as the t...
journal_title:Molecular psychiatry
pub_type: 杂志文章,多中心研究
doi:10.1038/sj.mp.4000881
更新日期:2001-07-01 00:00:00
abstract::Abnormalities in the density of neuroreceptors that regulate norepinephrine and serotonin release have been repeatedly reported in brains of suicide victims with mood disorders. Recently, the modulation of the [(35)S]GTPgammaS binding to G-proteins has been introduced as a suitable measure of receptor activity in post...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001067
更新日期:2002-01-01 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::Benzodiazepines facilitate the inhibitory actions of GABA by binding to γ-aminobutyric acid type A receptors (GABAARs), GABA-gated chloride/bicarbonate channels, which are the key mediators of transmission at inhibitory synapses in the brain. This activity underpins potent anxiolytic, anticonvulsant and hypnotic effec...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0100-y
更新日期:2018-09-01 00:00:00