A5039997190- Phosphodiesterase function and regulation
- Receptor Mechanisms and Signaling
- Renin-Angiotensin System Studies
- Neuroscience and Neuropharmacology Research
- Neuroendocrine regulation and behavior
- Neuropeptides and Animal Physiology
- Tryptophan and brain disorders
- Genetics and Neurodevelopmental Disorders
- Schizophrenia research and treatment
- Stress Responses and Cortisol
- Neurotransmitter Receptor Influence on Behavior
- Epigenetics and DNA Methylation
- 14-3-3 protein interactions
- MicroRNA in disease regulation
- Amino Acid Enzymes and Metabolism
- RNA modifications and cancer
- RNA Research and Splicing
- Bipolar Disorder and Treatment
- Circadian rhythm and melatonin
- Autism Spectrum Disorder Research
- Molecular Biology Techniques and Applications
- Immune Cell Function and Interaction
- Neurobiology and Insect Physiology Research
- Advanced Proteomics Techniques and Applications
- Neurological Disorders and Treatments
Johns Hopkins University
2013-2022
Johns Hopkins Medicine
2012-2022
Johns Hopkins Hospital
2015-2020
Institute of Behavioral Sciences
2007-2016
Pfizer (United States)
2012
Here, we report generation and characterization of Disrupted-In-Schizophrenia-1 (DISC1) genetically engineered mice as a potential model for major mental illnesses, such schizophrenia. DISC1 is promising genetic risk factor illnesses. In this transgenic model, dominant-negative form (DN-DISC1) expressed under the alphaCaMKII promoter. vivo MRI DN-DISC1 detected enlarged lateral ventricles particularly on left side, suggesting link to asymmetrical change in anatomy found brains patients with...
Defeat, Distress, and Glucocorticoids Understanding how individuals control emotions cope with stressful events is a major clinical concern of importance for the treatment psychiatric illnesses (see Perspective by McEwen ). Barik et al. (p. 332 ) discovered that aggressive defeat stress in mice caused glucocortioid release increased activity dopamine system. Deleting glucocorticoid receptors dopaminoceptive neurons completely prevented social avoidance usually follows defeat. How combination...
Guided by features of molecular, cellular, and circuit dysfunction affecting the prefrontal cortex in clinical investigations, we targeted studies a model for neuropsychiatric illness using transgenic mice expressing putative dominant-negative disrupted schizophrenia 1 (DN-DISC1). We detected marked augmentation GAPDH–seven absentia homolog Siah protein binding DISC1 mice, major hallmark nuclear GAPDH cascade that is activated response to oxidative stress. Furthermore, deficits were observed...
Significant advances have been made in understanding the role of disrupted‐in‐schizophrenia‐1 (DISC1) brain and accumulating findings suggest possible implication DISC1 regulation dopamine (DA) function. A mutation second exon at L100P leads to development schizophrenia‐related behavior mutant mice (DISC1‐L100P). We investigated here DA expression endophenotypes DISC1‐L100P genetic mouse model. The mutated resulted facilitation psychostimulant effect amphetamine assessed open field prepulse...
Neuregulin-1 (NRG1) and its receptor ErbB4 influence several processes of neurodevelopment, but the mechanisms regulating this signalling in mature brain are not well known. DISC1 is a multifunctional scaffold protein that mediates many cellular processes. Here we present functional relationship between NRG1-ErbB4 cortical interneurons. By cell type-specific gene modulation vitro vivo including mutant mouse model, demonstrate inhibits NRG1-induced activation signalling. This effect likely...
Imaging of the human brain has been an invaluable aid in understanding neuropsychopharmacology and, particular, role dopamine striatum mental illness. Here, we report a study genetic mouse model for major illness guided by results from imaging: systematic using small animal positron emission tomography (PET), autoradiography, microdialysis and molecular biology putative dominant-negative mutant DISC1 transgenic model. This showed augmented binding radioligands to D2 receptor (D2R) as well...
d-Amino acid oxidase (DAAO) catalyzes the oxidative deamination of d-amino acids including d-serine, a full agonist at glycine modulatory site <i>N</i>-methyl-d-aspartate (NMDA) receptor. To evaluate significance DAAO-mediated metabolism in pharmacokinetics oral plasma d-serine levels were measured both wild-type mice and transgenic lacking DAAO. Although rapidly diminished (<i>t</i><sub>½</sub> = 1.2 h), sustained drug over course 4 h > 10 h) observed Coadministration with...
We present results from a novel comparative approach to the study of mechanisms psychiatric disease. Previous work examined neural activity patterns in hippocampus freely behaving mouse model associated with schizophrenia, calcineurin knockout mouse. Here we genetically distinct that exhibits similar set behavioral phenotypes transgenic expressing putative dominant-negative DISC1 (DN-DISC1). Strikingly, principal finding earlier is replicated DN-DISC1 mice, is, selective increase numbers...
Quetiapine is an atypical neuroleptic with a pharmacological profile distinct from classic neuroleptics that function primarily via blockade of dopamine D2 receptors. In the United States, quetiapine currently approved for treating patients schizophrenia, major depression and bipolar I disorder. Despite its widespread use, cellular effects remain elusive. To address possible mechanisms, we chronically treated mice quetiapine, haloperidol or vehicle examined quetiapine-specific gene...