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 begun to catapult our knowledge of the genetic, molecular and cellular mechanisms in the brain that are linked to a variety of mental disorders as well as normal behavioral processes such as learning and memory. Moreover, the potential for transgenic technology to develop more precise animal models of specific human neuropsychiatric disorders will likely lead to the identification of novel targets for therapeutic intervention and facilitate the preclinical testing of new therapeutic agents. This article examines key issues and highlights recent developments pertaining to the transgenic modeling of neuropsychiatric disorders.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Campbell IL,Gold LHsubject
Has Abstractpub_date
1996-05-01 00:00:00pages
105-20issue
2eissn
1359-4184issn
1476-5578journal_volume
1pub_type
杂志文章,评审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::This Article was originally published under Nature Research's License to Publish, but has now been made available under a [CC BY 4.0] license. The PDF and HTML versions of the Article have been modified accordingly. ...
journal_title:Molecular psychiatry
pub_type: 已发布勘误
doi:10.1038/s41380-018-0327-7
更新日期:2019-09-01 00:00:00
abstract::Anxiety disorders are common, complex psychiatric disorders with twin heritabilities of 30-60%. We conducted a genome-wide association study of Lifetime Anxiety Disorder (ncase = 25 453, ncontrol = 58 113) and an additional analysis of Current Anxiety Symptoms (ncase = 19 012, ncontrol = 58 113). The liability scale c...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0559-1
更新日期:2020-12-01 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.2016.107. ...
journal_title:Molecular psychiatry
pub_type: 杂志文章,已发布勘误
doi:10.1038/mp.2017.203
更新日期:2018-01-01 00:00:00
abstract::Folic acid supplementation confers modest benefit in schizophrenia, but its effectiveness is influenced by common genetic variants in the folate pathway that hinder conversion to its active form. We examined physiological and clinical effects of l-methylfolate, the fully reduced and bioactive form of folate, in schizo...
journal_title:Molecular psychiatry
pub_type: 杂志文章,随机对照试验
doi:10.1038/mp.2017.41
更新日期:2018-02-01 00:00:00
abstract::Amyloid-β peptide (Aβ) accumulation in the brain is a hallmark of Alzheimer's Disease. An important mechanism of Aβ clearance in the brain is uptake and degradation by microglia. Presenilin 1 (PS1) is the catalytic subunit of γ-secretase, an enzyme complex responsible for the maturation of multiple substrates, such as...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-0856-8
更新日期:2020-08-13 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::In recent years, numerous studies of gene regulation mechanisms have emerged in neuroscience. Epigenetic modifications, described as heritable but reversible changes, include DNA methylation, DNA hydroxymethylation, histone modifications and noncoding RNAs. The pathogenesis of psychiatric disorders, such as bipolar di...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/mp.2016.123
更新日期:2016-11-01 00:00:00
abstract::This paper summarizes recent research on mitochondrial DNA (mtDNA)--which might be described as the "other, forgotten genome". Recent studies suggest the possible pathophysiological significance of mtDNA in schizophrenia and neurodegenerative and mood disorders. Decreased activity of the mitochondrial electron transpo...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/sj.mp.4000926
更新日期:2001-11-01 00:00:00
abstract::Identifying biological mechanisms through which the experience of adversity emerges as individual risk for mental illness is an important step toward developing strategies for personalized treatment and, ultimately, prevention. Preclinical studies have identified epigenetic modification of gene expression as one such ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2016.82
更新日期:2017-02-01 00:00:00
abstract::Epidermal growth factor (EGF) comprises a structurally related family of proteins containing heparin-binding EGF-like growth factor (HB-EGF) and transforming growth factor alpha (TGFalpha) that regulates the development of dopaminergic neurons as well as monoamine metabolism. We assessed the contribution of EGF to sch...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001081
更新日期:2002-01-01 00:00:00
abstract::Depression is a heritable disorder that is often precipitated by stress. Abnormalities of the stress-reactive hypothalamic-pituitary-adrenal (HPA) axis are also common in depressed patients. In animal models, the forced swim test (FST) is the most frequently used test of depressive-like behavior. We have used a propos...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001255
更新日期:2003-04-01 00:00:00
abstract::Bipolar affective disorder is one of the most common mental illnesses with a population prevalence of approximately 1%. The disorder is genetically complex, with an increasing number of loci being implicated through genetic linkage studies. However, the specific genetic variations and molecules involved in bipolar sus...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001113
更新日期:2002-01-01 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::Contemporary models of psychosis suggest that a continuum of severity of psychotic symptoms exists, with subthreshold psychotic experiences (PEs) potentially reflecting some genetic and environmental risk factors shared with clinical psychosis. Thus, identifying abnormalities in brain activity that manifest across thi...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-00983-1
更新日期:2021-01-18 00:00:00
abstract::Chromosome 1q has been implicated in the etiology of schizophrenia in several independent studies. However, the peak linkage findings have been dispersed over a large chromosomal region, with negative findings in this region also being reported. Our group has previously observed linkage on chromosome 1q42, maximizing ...
journal_title:Molecular psychiatry
pub_type: 临床试验,杂志文章
doi:10.1038/sj.mp.4001536
更新日期:2004-11-01 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::Neurotrophins promote neuronal survival and synaptic plasticity via activating the tropomyosin receptor kinases. BDNF and its high-affinity receptor TrkB are reduced in Alzheimer's disease (AD), contributing to progressive cognitive decline. However, how the signaling mediates AD pathologies remains incompletely under...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-00863-8
更新日期:2020-08-11 00:00:00
abstract::Lipids are essential to brain functions, yet they remain largely unexplored. Here we investigated the lipidome composition of prefrontal cortex gray matter in 396 cognitively healthy individuals with ages spanning 100 years, as well as 67 adult individuals diagnosed with autism (ASD), schizophrenia (SZ), and Down synd...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0200-8
更新日期:2020-11-01 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::This article was originally published under standard licence, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the paper have been modified accordingly. ...
journal_title:Molecular psychiatry
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41380-018-0301-4
更新日期:2019-03-01 00:00:00
abstract::With the fast advance of connectome imaging techniques, we have the opportunity of mapping the human brain pathways in vivo at unprecedented resolution. In this article we review the current developments of diffusion magnetic resonance imaging (MRI) for the reconstruction of anatomical pathways in connectome studies. ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.92
更新日期:2017-09-01 00:00:00
abstract::Cariprazine (CAR) is a strong inhibitor of the Dhcr7 enzyme, the last enzyme in the cholesterol biosynthesis pathway. We assessed the effects of CAR on maternally exposed Dhcr7+/- and wild-type mouse offspring, and tested the biochemical effects of CAR in human serum samples. Dhcr7+/- and wild-type time-pregnant mice ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-0801-x
更新日期:2020-11-01 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::Several studies suggest that decreased expression of presynaptic proteins may be characteristic of schizophrenia. We examined one such protein, synapsin, in schizophrenia and bipolar disorder. Samples of hippocampal tissue from controls (n = 13), patients with schizophrenia (n = 16), or bipolar disorder (n = 6), and s...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001158
更新日期:2002-01-01 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::There are well-replicated, independent lines of evidence supporting a role for corticotropin-releasing hormone (CRH) in the pathophysiology of depression. CRH receptor 1 (CRHR1), which we first mapped in the brain in 1994, has been implicated in the treatment of depression and anxiety. We studied the association of CR...
journal_title:Molecular psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/sj.mp.4001587
更新日期:2004-12-01 00:00:00
abstract::Studies using tissue obtained at autopsy suggest that changes in cholinergic neurons could be important in the pathology of schizophrenia.1-4 We have previously reported a decrease in [3H]pirenzepine binding5 and [3H]AF-DX 384 binding6 to caudate-putamen (CP) from subjects who had schizophrenia. Under the conditions c...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000684
更新日期:2000-03-01 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