A5009553136- Neuroscience and Neuropharmacology Research
- Tryptophan and brain disorders
- Receptor Mechanisms and Signaling
- Neuroendocrine regulation and behavior
- Neurotransmitter Receptor Influence on Behavior
- Stress Responses and Cortisol
- RNA regulation and disease
- Birth, Development, and Health
- RNA Research and Splicing
- Amino Acid Enzymes and Metabolism
- Genetics and Neurodevelopmental Disorders
- Diet and metabolism studies
- Pharmaceutical studies and practices
- Phagocytosis and Immune Regulation
- Memory and Neural Mechanisms
- Neural dynamics and brain function
- Immune cells in cancer
- RNA modifications and cancer
- Maternal Mental Health During Pregnancy and Postpartum
- Epigenetics and DNA Methylation
- Cannabis and Cannabinoid Research
- Cell Image Analysis Techniques
- Hearing, Cochlea, Tinnitus, Genetics
- MicroRNA in disease regulation
- Protein Structure and Dynamics
University of Haifa
2016-2025
Brain (Germany)
2024
Columbia University
2010-2021
New York Psychoanalytic Society and Institute
2009-2021
Carmel (Israel)
2016-2021
New York State Psychiatric Institute
2012-2021
Sheba Medical Center
2014
Tel Aviv University
2002-2007
Dopamine neurons in the ventral tegmental area use glutamate as a cotransmitter. To elucidate behavioral role of cotransmission, we targeted glutamate-recycling enzyme glutaminase (gene Gls1). In mice with dopamine transporter (Slc6a3)-driven conditional heterozygous (cHET) reduction Gls1 their neurons, neuron survival and transmission were unaffected, while cotransmission at phasic firing frequencies was reduced, enabling selective focus on cotransmission. The showed normal emotional motor...
Abstract Neuronal nitric oxide synthase (nNOS, gene name Nos1) orchestrates the synthesis of (NO) within neurons, pivotal for diverse neural processes encompassing synaptic transmission, plasticity, neuronal excitability, learning, memory, and neurogenesis. Despite its significance, precise regulation nNOS activity across distinct types remains incompletely understood. Erb-b2 receptor tyrosine kinase 4 (ErbB4), selectively expressed in GABAergic interneurons activated by ligand neuregulin 1...
<title>Abstract</title> Social stress has long-term behavioral and physiological consequences, studies in male rodents show that it alters sperm miRNA expression behavior offspring. The direct transgenerational impact of social females on brain germline not been studied, its effect offspring phenotypes remains unknown. In this study, we compared the adolescent female rats (F0) their three generations forward (F1-F3). We found Isolation (SI) Food Water Deprivation (FWD) during adolescence...
Adenosine-to-inosine (A-to-I) RNA editing is an epigenetic modification catalyzed by adenosine deaminases acting on (ADARs), and especially prevalent in the brain. We used highly accurate microfluidics-based multiplex PCR sequencing (mmPCR-seq) technique to assess effects of development environmental stress A-to-I at 146 pre-selected, conserved sites rat prefrontal cortex amygdala. Furthermore, we asked whether changes can be observed offspring stress-exposed rats. In parallel, assessed...
Brain imaging has revealed that the CA1 subregion of hippocampus is hyperactive in prodromal and diagnosed patients with schizophrenia (SCZ), glutamate a driver this hyperactivity. Strikingly, mice deficient synthetic enzyme glutaminase have hypoactivity SCZ-resilience profile, implicating glutamate-metabolizing enzymes. To address further, we examined brain-wide deficit dehydrogenase (GDH), encoded by Glud1, which should lead to excess due reduced metabolism astrocytes. We found...
Early life stress (ELS) increases predisposition to depression. We compared the effects of treatment with fatty acid amide hydrolase (FAAH) inhibitor URB597, and selective serotonin reuptake paroxetine, on ELS-induced depressive-like behavior expression microRNAs (miRs) associated depression in medial prefrontal cortex (mPFC), hippocampal CA1 area, lateral habenula dorsal raphe rats. also examined mRNA serotonergic (htr1a slc6a4) endocannabinoid (cnr1, cnr2 faah) targets mPFC following ELS...
Genetic pharmacotherapy is an early drug development strategy for the identification of novel CNS targets in mouse models prior to specific ligands. Here first time, we have implemented this address potential therapeutic value a glutamate-based schizophrenia involving inhibition glutamate recycling enzyme phosphate-activated glutaminase. Mice constitutively heterozygous GLS1, gene encoding glutaminase, manifest resilience phenotype, key dimension which attenuated locomotor response...
Stress during development affects maternal behavior and offspring phenotypes. in adolescence is particularly consequential on brain maturation, implicated several psychiatric disorders. We previously showed that pre-reproductive stress (PRS) female adolescent rats corticotropin releasing hormone receptor 1 (CRHR1) expression first- (F1) second- (F2) generation offspring. further phenotypes are partially reversed by post-stress treatment with fluoxetine (FLX) or the CRHR1 antagonist NBI27914...
Current animal models of antipsychotic activity that have the capacity to dissociate between typical and atypical drugs (APDs) two drawbacks: they require previous administration a psychotomimetic drug, achieve dissociation by demonstrating effectiveness but not APDs, thus losing specificity selectivity for APDs. The present experiments were designed solve these problems using non-pharmacological tests: latent inhibition (LI), in which potentiation deleterious effects non-reinforced stimulus...
Early Alzheimer's disease (AD) is characterized by memory loss and hippocampal atrophy with relative sparing of basal ganglia. Activation glutamate NMDA receptors in the hippocampus an important step formation. We measured density samples hippocampus, entorhinal cortex ganglia obtained from subjects who died pathologically confirmed AD age- sex- matched non-demented controls. found significant decreases receptor but not Loss was significantly correlated neuropathological progression as...
Glutamate abnormalities in the medial prefrontal cortex (mPFC) are associated with cognitive deficits. We previously showed that homozygous deletion of CNS glutamate dehydrogenase 1 (Glud1), a metabolic enzyme critical for metabolism, leads to schizophrenia-like behavioral and increased mPFC glutamate; mice heterozygous Glud1 (C-Glud1+/- mice) no or molecular abnormalities. Here, we examined protracted effects mild injection stress on C-Glud1+/- mice. found spatial reversal learning...
We describe here a coordinated brain imaging and animal models approach in which we have shown that the hippocampal CA1 region is principal node schizophrenia pathogenesis identified novel treatment to disorder based on inhibition of glutamate release. To identify biomarkers, focused putative prodromal period, typically lasting few years, preceding first onset psychosis. About one-third high-risk cohort followed prospectively for 2.5 years will progress threshold psychosis, making it...
Abstract Glutaminase‐deficient mice (GLS1 hets), with reduced glutamate recycling, have a focal reduction in hippocampal activity, mainly CA1, and manifest behavioral neurochemical phenotypes suggestive of schizophrenia resilience. To address the basis for hypoactivity, we examined synaptic plastic mechanisms receptor expression. Although baseline strength was unaffected Schaffer collateral inputs to found that long‐term potentiation attenuated. In wild‐type (WT) mice, GLS1 gene expression...
Abstract Neuronal epigenomes, including chromosomal loopings moving distal cis -regulatory elements into proximity of target genes, could serve as molecular proxy linking present-day-behaviour to past exposures. However, longitudinal assessment chromatin state is challenging, because conventional chromosome conformation capture assays essentially provide single snapshots at a given time point, thus reflecting genome organization the brain harvest and therefore are non-informative about past....