A5079479189- Tryptophan and brain disorders
- Stress Responses and Cortisol
- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Genetics and Neurodevelopmental Disorders
- Receptor Mechanisms and Signaling
- Treatment of Major Depression
- Epigenetics and DNA Methylation
- Neuropeptides and Animal Physiology
- Genomics and Chromatin Dynamics
- Nuclear Receptors and Signaling
- Genetics, Aging, and Longevity in Model Organisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience, Education and Cognitive Function
- Histone Deacetylase Inhibitors Research
- Adipose Tissue and Metabolism
- Neurological Disorders and Treatments
- Platelet Disorders and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Immune Cell Function and Interaction
- Early Childhood Education and Development
- Cannabis and Cannabinoid Research
- Protein Degradation and Inhibitors
- Reading and Literacy Development
- RNA Interference and Gene Delivery
Yale University
2010-2024
Allen Institute for Brain Science
2016-2024
Icahn School of Medicine at Mount Sinai
2016-2024
Semmelweis University
2017
Gedeon Richter (Hungary)
2017
Allergan (United States)
2017
Institute of Cognitive Neuroscience and Psychology
2017
Hungarian Academy of Sciences
2017
Des Moines University
2017
Mental Health Research Canada
2017
Background:Recent studies demonstrate that the rapid antidepressant ketamine increases spine number and function in medial prefrontal cortex (mPFC), these effects are dependent on activation of glutamate α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors brain-derived neurotrophic factor (BDNF). In vitro also show AMPA stimulates BNDF release via L-type voltage-dependent calcium channels (VDCC).
More than a normal neurotransmitter The molecular mechanisms underlying the persistence of addiction remain largely unclear. Lepack et al. found that, with cocaine exposure, there is an intracellular accumulation dopamine in neurons brain region called ventral tegmental area (see Perspective by Girault). Dopamine associates chromatin to initiate previously unknown form epigenetic regulation dopaminylation. This modification has impact on function and, consequently, dopaminergic action...
Recent studies demonstrate that ketamine, a fast-acting antidepressant, rapidly activates the mammalian target of rapamycin (mTOR) and increases synaptogenesis in prefrontal cortex. Because side-effect abuse potential ketamine we are investigating alternative agents produce similar effects. Here, single dose LY 341495, an mGluR₂/₃ antagonist, produces ketamine-like biochemical behavioural actions. 341495 administration (1 h) mTOR pathway (mTOR, p70S6K, 4E-BP1) subsequently (24 h later)...
Background Evidence continues to build suggesting that the GABAergic neurotransmitter system is altered in brains of patients with major depressive disorder. However, there little information available related extent these changes or potential mechanisms associated alterations. As stress a well-established precipitant episodes, we sought explore impact chronic on interneurons. Methods Using western blot analyses and quantitative real-time polymerase chain reaction, assessed effects...
Mood disorders are an enigmatic class of debilitating illnesses that affect millions individuals worldwide. While chronic stress clearly increases incidence levels mood disorders, including major depressive disorder (MDD), stress-mediated disruptions in brain function precipitate these remain largely elusive. Serotonin-associated antidepressants (ADs) the first line therapy for many with symptoms, yet low remission rates and delays between treatment symptomatic alleviation have prompted...
Decreased neuronal dendrite branching and plasticity of the hippocampus, a limbic structure implicated in mood disorders, is thought to contribute symptoms depression. However, mechanisms underlying this effect, as well actions antidepressant treatment, remain poorly characterized. Here, we show that hippocampal expression neuritin, an activity-dependent gene regulates plasticity, decreased by chronic unpredictable stress (CUS) treatment reverses effect. We also viral-mediated neuritin...
Cariprazine, a D3-preferring dopamine D2/D3 receptor partial agonist, is new antipsychotic drug recently approved in the United States for treatment of schizophrenia and bipolar mania. We demonstrated that cariprazine also has significant antianhedonic-like effects rats subjected to chronic stress; however, exact mechanism action cariprazine’s antidepressant-like properties not known. Thus, this study we examined whether are mediated by D3 receptors. Wild-type D3-knockout mice were exposed...
Depression is a prevalent neuropsychiatric disorder that affects an estimated 350 million people worldwide. Currently available treatments for depression are lacking in both speed of onset and efficacy. Recent pharmacological efforts have targeted the glutamatergic neurotransmitter system using N-methyl-D-aspartate (NMDA) receptor antagonist ketamine to produce rapid robust antidepressant effects, however widespread clinical use limited due side effects abuse liability. More recently, work...
Significance The molecular pathophysiology associated with depression remains largely unknown. Recent evidence suggests that signaling pathways downstream of mechanistic target rapamycin complex 1, such as p70 S6 kinase 1 (S6K1), can lead to structural changes in the medial prefrontal cortex (mPFC) rats, which are antidepressant responses. We used a viral-mediated approach control S6K1 activity mPFC. Enhanced produced antidepressant-like effects and resilience chronic stress, whereas...
Significance Although mutations in the neuroligin-3 and neuroligin-4 genes are implicated autism syndromes, very little is known about contribution of neuroligin-2 to neuropsychiatric disease states. We report a decrease gene expression postmortem nucleus accumbens (NAc) depressed patients. Reverse translation this finding chronic social defeat stress, an animal model depression that enables investigation both susceptibility resiliency mechanisms, uncovers important functional role for NAc...
Persistent transcriptional events in ventral tegmental area (VTA) and other reward relevant brain regions contribute to enduring behavioral adaptations that characterize substance use disorder. Recent data from our laboratory indicate aberrant accumulation of the newly discovered histone post-translational modification (PTM), H3 dopaminylation at glutamine 5 (H3Q5dop), contributes significantly cocaine-seeking behavior following prolonged periods abstinence. It remained unclear, however,...
Abstract Reductions of astroglia expressing glial fibrillary acidic protein (GFAP) are consistently found in the prefrontal cortex (PFC) patients with depression and rodent chronic stress models. Here, we examine consequences PFC GFAP+ cell depletion activity enhancement on depressive-like behaviors rodents. Using viral expression diphtheria toxin receptor cells, which allows experimental these cells following administration, demonstrated that induced anhedonia-like behavior within 2 days...
Significance Human major depressive disorder is a chronic remitting syndrome that affects millions of individuals worldwide; however, the molecular mechanisms mediating this remain elusive. Here, using unique combination epigenome-wide and behavioral analyses, we demonstrate role for histone variant dynamics in nucleus accumbens (NAc)—a critical brain center reward mood—contributing to stress susceptibility mice. These studies, which also blockade aberrant NAc promotes resilience stress,...
Enduring patterns of epigenomic and transcriptional plasticity within the mesolimbic dopamine system contribute importantly to persistent behavioral adaptations that characterize substance use disorders (SUD). While drug addiction has long been thought as a disorder (DA) neurotransmission, therapeutic interventions targeting receptor mediated DA-signaling have not yet resulted in efficacious treatments. Our laboratory recently identified non-canonical, neurotransmission-independent signaling...
Abstract With an incidence of ~1 in 800 births, Down syndrome (DS) is the most common chromosomal condition linked to intellectual disability worldwide. While genetic basis DS has been identified as a triplication chromosome 21 (HSA21), genes encoded from HSA21 that directly contribute cognitive deficits remain incompletely understood. Here, we found HSA21-encoded chromatin effector, BRWD1 , was upregulated neurons derived iPS cells individual with and brain trisomic mice. We showed...
Disruptions in the development of neocortex are associated with cognitive deficits humans and other mammals. Several genes contribute to neocortical development, research into behavioral phenotype specific gene manipulations is advancing rapidly. Findings include evidence that variants human DYX1C1 may be an increased risk developmental dyslexia. Concurrent has shown rat homolog for this modulates critical parameters early cortical including neuronal migration. Moreover, recent studies have...
Proteasomal-regulated chromatin remodeler mediates cocaine relapse during abstinence.
ABSTRACT Background Major depressive disorder (MDD), along with related mood disorders, is a debilitating illness that affects millions of individuals worldwide. While chronic stress increases incidence levels stress-mediated disruptions in brain function precipitate these illnesses remain elusive. Serotonin-associated antidepressants (ADs) the first line therapy for many symptoms, yet low remission rates and delays between treatment symptomatic alleviation have prompted skepticism regarding...