THC Treatment Alters Glutamate Receptor Gene Expression in Human Stem Cell-Derived Neurons
Given the cognitive and behavioral effects following in utero #x0394;9-tetrahydrocannabinol (THC) exposure that have been reported in humans and rodents, it is critical to understand the precise consequences of THC on developing human neurons. Here, we utilize excitatory neurons derived from human-induced pluripotent stem cells (hiPSCs), and report that in vitro THC exposure reduced expression of glutamate receptor subunit genes (GRIA1,GRIA2, GRIN2A, andGRIN2B). By expanding these studies across hiPSC-derived neurons from individuals with a variety of genotypes, we believe that a hiPSC-based model will facilitate studies o...
Source: Molecular Neuropsychiatry - October 25, 2017 Category: Neuroscience Source Type: research
Circuitry-Based Human Neuroanatomy for the Next Generation in Psychiatry and Neuroscience
Mol Neuropsychiatry 2017;3:92-96 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - October 25, 2017 Category: Neuroscience Source Type: research
Insulin Signaling Deficiency Produces Immobility in Caenorhabditis elegans That Models Diminished Motivation States in Man and Responds to Antidepressants
Defects in insulin signaling have been reported in schizophrenia and major depressive disorder, which also share certain negative symptoms such as avolition, anhedonia, and apathy. These symptoms reflect diminished motivational states, which have been modeled in rodents as increased immobility in the forced swimming test. We have discovered that loss-of-function mutations in the insulin receptor (daf-2) and syntaxin (unc-64) genes inCaenorhabditis elegans, brief food deprivation, and exposure to DMSO produce immobility and avolition in non-dauer adults. The animals remain responsive to external stimuli; however, they fail ...
Source: Molecular Neuropsychiatry - October 25, 2017 Category: Neuroscience Source Type: research
Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature
We present recent advances from preclinical and clinical studies that further support the role of PKC. Moreover, we discuss the role of PKC on synaptogenesis and neuroplasticity in the context of BD. The recent development of animal models of BD, such as stimulant-treated and paradoxical sleep deprivation, and the ability to intervene pharmacologically provide further insights into the involvement of PKC in BD. In addition, the effect of PKC inhibitors, such as tamoxifen, in the resolution of manic symptoms in patients with BD further points in that direction. Furthermore, a wide variety of growth factors influence neurotr...
Source: Molecular Neuropsychiatry - October 25, 2017 Category: Neuroscience Source Type: research
Insulin Signaling Deficiency Produces Immobility in Caenorhabditis elegans That Models Diminished Motivation States in Man and Responds to Antidepressants
Defects in insulin signaling have been reported in schizophrenia and major depressive disorder, which also share certain negative symptoms such as avolition, anhedonia, and apathy. These symptoms reflect diminished motivational states, which have been modeled in rodents as increased immobility in the forced swimming test. We have discovered that loss-of-function mutations in the insulin receptor (daf-2) and syntaxin (unc-64) genes inCaenorhabditis elegans, brief food deprivation, and exposure to DMSO produce immobility and avolition in non-dauer adults. The animals remain responsive to external stimuli; however, they fail ...
Source: Molecular Neuropsychiatry - September 21, 2017 Category: Neuroscience Source Type: research
Insulin Signaling Deficiency Produces Immobility in < b > < i > Caenorhabditis elegans < /i > < /b > That Models Diminished Motivation States in Man and Responds to Antidepressants
Defects in insulin signaling have been reported in schizophrenia and major depressive disorder, which also share certain negative symptoms such as avolition, anhedonia, and apathy. These symptoms reflect diminished motivational states, which have been modeled in rodents as increased immobility in the forced swimming test. We have discovered that loss-of-function mutations in the insulin receptor (daf-2) and syntaxin (unc-64) genes inCaenorhabditis elegans, brief food deprivation, and exposure to DMSO produce immobility and avolition in non-dauer adults. The animals remain responsive to external stimuli; however, they fail ...
Source: Molecular Neuropsychiatry - September 20, 2017 Category: Neuroscience Source Type: research
Circuitry-Based Human Neuroanatomy for the Next Generation in Psychiatry and Neuroscience
Mol Neuropsychiatry 2017;3:92-96 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - September 6, 2017 Category: Neuroscience Source Type: research
THC Treatment Alters Glutamate Receptor Gene Expression in Human Stem Cell-Derived Neurons
Given the cognitive and behavioral effects following in utero #x0394;9-tetrahydrocannabinol (THC) exposure that have been reported in humans and rodents, it is critical to understand the precise consequences of THC on developing human neurons. Here, we utilize excitatory neurons derived from human-induced pluripotent stem cells (hiPSCs), and report that in vitro THC exposure reduced expression of glutamate receptor subunit genes (GRIA1,GRIA2, GRIN2A, andGRIN2B). By expanding these studies across hiPSC-derived neurons from individuals with a variety of genotypes, we believe that a hiPSC-based model will facilitate studies o...
Source: Molecular Neuropsychiatry - July 19, 2017 Category: Neuroscience Source Type: research
Altered Expression of Endoplasmic Reticulum Stress-Related Genes in the Middle Frontal Cortex of Subjects with Autism Spectrum Disorder
The endoplasmic reticulum (ER) is an important organelle responsible for the folding and sorting of proteins. Disturbances in ER homeostasis can trigger a cellular response known as the unfolded protein response, leading to accumulation of unfolded or misfolded proteins in the ER lumen called ER stress. A number of recent studies suggest that mutations in autism spectrum disorder (ASD)-susceptible synaptic genes induce ER stress. However, it is not known whether ER stress-related genes are altered in the brain of ASD subjects. In the present study, we investigated the mRNA expression of ER stress-related genes (ATF4, ATF6,...
Source: Molecular Neuropsychiatry - July 18, 2017 Category: Neuroscience Source Type: research
WNT/ β-Catenin Pathway and Epigenetic Mechanisms Regulate the Pitt-Hopkins Syndrome and Schizophrenia Risk Gene < b > < i > TCF4 < /i > < /b >
Genetic variation within the transcription factorTCF4 locus can cause the intellectual disability and developmental disorder Pitt-Hopkins syndrome (PTHS), whereas single-nucleotide polymorphisms within noncoding regions are associated with schizophrenia. These genetic findings position TCF4 as a link between transcription and cognition; however, the neurobiology of TCF4 remains poorly understood. Here, we quantitated multiple distinctTCF4 transcript levels in human induced pluripotent stem cell-derived neural progenitors and differentiated neurons, and PTHS patient fibroblasts. We identify two classes of pharmacological tr...
Source: Molecular Neuropsychiatry - July 13, 2017 Category: Neuroscience Source Type: research
The Nuclear Proteome of White and Gray Matter from Schizophrenia Postmortem Brains
Schizophrenia (SCZ) is a serious neuropsychiatric disorder that manifests through several symptoms from early adulthood. Numerous studies over the last decades have led to significant advances in increasing our understanding of the factors involved in SCZ. For example, mass spectrometry-based proteomic analysis has provided important insights by uncovering protein dysfunctions inherent to SCZ. Here, we present a comprehensive analysis of the nuclear proteome of postmortem brain tissues from corpus callosum (CC) and anterior temporal lobe (ATL). We show an overview of the role of deregulated nuclear proteins in these two ma...
Source: Molecular Neuropsychiatry - June 16, 2017 Category: Neuroscience Source Type: research
Low-Density Neuronal Cultures from Human Induced Pluripotent Stem Cells
We describe a differentiation protocol to generate low-density neuronal cultures ( ∼2,500 neurons/cm2) from human iPSC-derived neural stem cells/early neural progenitor cells. We generated low-density cultures using cells from 3 individuals. We also evaluated the morphometric features of neurons derived from 2 of these individuals, one harboring a microdeletion on chromosome 15q11.2 and the other without the microdeletion. An approximately 7.5-fold increase in the density of dendritic filopodia was observed in the neurons with the microdeletion, consistent with previous reports. Low-density neuronal cultures enable facil...
Source: Molecular Neuropsychiatry - June 16, 2017 Category: Neuroscience Source Type: research
Complement C3 Expression Is Decreased in Autism Spectrum Disorder Subjects and Contributes to Behavioral Deficits in Rodents
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with hallmark symptoms including social deficits, communication deficits and repetitive behaviors. Accumulating evidence suggests a potential role of the immune system in the pathophysiology of ASD. The complement system represents one of the major effector mechanisms of the innate immune system, and regulates inflammation, and orchestrates defense against pathogens. However, the role of CNS complement system in ASD is not well understood. In the present study, we found a significant increase in C2, C5, and MASP1, but a decrease in C1q, C3, and C4 mRNA levels ...
Source: Molecular Neuropsychiatry - May 4, 2017 Category: Neuroscience Source Type: research
A Preliminary Study of the Opioid System and Personality Traits Using Positron Emission Tomography
Conclusions: While preliminary, the results of this study suggest that the expression of Neuroticism and Extraversion is related to baseline function of the opioid neurotransmitter system in the insular cortex. These findings may help elucidate the neural mechanisms underlying the expression of personality traits, particularly those implicated in affective processing.Mol Neuropsychiatry 2017;3:12-18 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - March 10, 2017 Category: Neuroscience Source Type: research
