A5004545899- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- CRISPR and Genetic Engineering
- Neuroscience and Neuropharmacology Research
- RNA regulation and disease
- Genetics and Neurodevelopmental Disorders
- Parkinson's Disease Mechanisms and Treatments
- Pluripotent Stem Cells Research
- Signaling Pathways in Disease
- Nicotinic Acetylcholine Receptors Study
- Congenital heart defects research
- Nuclear Receptors and Signaling
- Nerve injury and regeneration
- Schizophrenia research and treatment
- Autism Spectrum Disorder Research
- RNA Research and Splicing
- Musculoskeletal pain and rehabilitation
- Single-cell and spatial transcriptomics
- Tryptophan and brain disorders
- Birth, Development, and Health
- Stress Responses and Cortisol
- Myofascial pain diagnosis and treatment
- 14-3-3 protein interactions
- Neurogenesis and neuroplasticity mechanisms
- Vibration and Dynamic Analysis
University of Luxembourg
2020-2024
Luxembourg Institute of Health
2023
University of California, San Francisco
2021-2022
Gladstone Institutes
2021-2022
University of Toronto
2000-2013
Centre for Addiction and Mental Health
2009-2013
Muscular Dystrophy Canada
2013
Emory University
2008-2010
Canada Research Chairs
2006-2010
University of New Brunswick
2010
Parkinson's disease (PD) is a complex neurodegenerative disorder without cure. The onset of PD symptoms corresponds to 50% loss midbrain dopaminergic (mDA) neurons, limiting early-stage understanding PD. To shed light on early development, we study time series scRNA-seq datasets mDA neurons obtained from patient-derived induced pluripotent stem cell differentiation. We develop new data integration method based Non-negative Matrix Tri-Factorization that integrates these with molecular...
A biomechanical analysis was performed of lifting before and after fatiguing the quadriceps muscles. The hypothesis tested that when muscles were fatigued lifter would change technique from more a squat (leg) lift to stoop (back) decrease demand on broadly supported, three variables changed significantly with fatigue: trunk angular velocity, which increased, knee moment integral hip angles, both decreased. These changes are all consistent toward technique. fact muscle fatigue underlines...
Abstract Parkinson’s disease (PD) is the second-most prevalent neurodegenerative disorder, characterized by loss of dopaminergic neurons (mDA) in midbrain. The underlying mechanisms are only partly understood and there no treatment to reverse PD progression. Here, we investigated mechanism using mDA differentiated from human induced pluripotent stem cells (hiPSCs) carrying ILE368ASN mutation within PINK1 gene, which strongly associated with PD. Single-cell RNA sequencing (RNAseq) gene...
In searching for genes dysregulated in schizophrenia, we measured the expression of two splice variants calcium/calmodulin-dependent protein kinase II (CaMKIIα and CaMKIIβ) postmortem frontal cerebral cortex tissues from patients who had died with bipolar disorder, or severe depression. The mRNA levels these were by real–time Quantitative PCR, using an Mx4000 instrument. values CaMKIIα CaMKIIβ normalized β-glucuronidase tissues. was significantly elevated depression 29%. schizophrenia 27%,...
Emerging evidence indicates that the DRD1-BDNF-DRD3 cluster plays an important role in nicotine addiction. We have performed association analysis of 42 SNPs within these genes with cigarette consumption a group 341 schizophrenia patients. The ACCG haplotype consisting four BDNF markers (Val66Met (rs6265), rs11030104, rs2049045 and rs7103411) showed risk smoking (p = 0.0002). Both DRD1 tested (rs4532 rs686) DRD3 marker (rs1025398) quantity tobacco smoked 0.01, 0.005 0.002, respectively). Our...
Whole genome scan studies have recently identified the NRXN1 and NRXN3 genes as potential contributing factors in risk for nicotine addiction. We genotyped 15 single nucleotide polymorphisms (SNPs) spanning 195 unrelated patients with schizophrenia whom information about their smoking status number of cigarettes smoked per day (CPD) was obtained. The marker rs1004212 significantly associated quantity tobacco smoked. Individuals homozygous C allele more than heterozygous individuals. found no...
Dopamine D2 receptors exist in both low- and high-affinity states (D2High), the latter being functionally relevant state. Cocaine self-administration produces an increase D2High, a phenomenon that could explain why cocaine administration results hypersensitivity to dopamine, even though drug addicts were found have decreased number of striatal dopamine receptors. As nicotine acts through same mesocortical dopaminergic signaling pathways as other stimulant drugs, which are known levels we...
The cerebral frontal cortex of patients who had schizophrenia shows elevated levels RNA for calcium/calmodulin-dependent protein kinase II beta (CaMKIIbeta). In addition, recent research that animal models schizophrenia, such as amphetamine-sensitized rats, consistently show D2 receptors in their high-affinity state (D2(High)), the major target antipsychotic medication. present study was done, therefore, to examine whether an alteration CaMKIIbeta could lead altered D2(High) receptors. We...
Abstract Because abnormal development of striatal neurons is thought to be the part pathology underlying major psychiatric illnesses, we studied expression pattern genes involved in and comprising key striatal‐specific pathways, during an active maturation period, first two postnatal weeks rat. This period parallels human second trimester, when prenatal stress though lead increased risk for neuropsychiatric disorders. To identify this developmental process, used subtractive hybridization,...
<h3>Background:</h3> Carriers of the <i>FMR1</i> premutation allele are at a significantly increased risk for late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS). This disorder is distinct from X (FXS) in its molecular aetiology and clinical presentation. The primary features FXTAS intention tremor gait ataxia. Associated include parkinsonism, neuropsychological dysfunction, autonomic dysfunction peripheral neuropathy. <h3>Aim:</h3> To investigate...
Schizophrenia and bipolar disorder are associated with dopamine neurotransmission show high comorbidity tobacco dependence. Recent evidence indicates that the family of NR4A orphan nuclear receptors, which expressed in neurons dopaminoceptive brain areas, may play a role dopamine-mediated effects. We have, therefore, analysed association six single nucleotide polymorphisms (SNPs) within three genes belonging to receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) NR4A3...
Abstract The goal of this study was to determine whether two stressors commonly used model aspects neuropsychiatric disease in rats have an additive effect on striatal dopamine type 2 receptor (D2R) expression, a key player the etiology disease. Animals subjected early postnatal stress show alterations function dopaminergic system thought be mediated by stress‐induced glucocorticoid release. Subsequent during puberty is known further impact and result hyperactivity analogous schizophrenia....
Abstract Recent studies have shown that the elevation in calcium/calmodulin‐dependent protein kinase II (CaMKII) may play an important role amphetamine‐induced dopamine release, as well increase of D2 receptor high‐affinitystates psychosis. Because amphetamine sensitization is a widely used animal model psychosis or schizophrenia, we investigated whether results overall α and β subunits CaMKII. To answer this question, measured CaMKII subunit mRNA expression using Real‐Time Quantitative PCR...
Recent evidence has identified the NR4A1 (NUR77, NGFI-B) gene as a strong candidate for involvement in tardive dyskinesia (TD). We have investigated association of six single nucleotide polymorphisms within NR4A family genes with TD sample 171 patients schizophrenia Caucasian descent. The polymorphism (SNP) marker rs2603751 showed nominal risk TD, well extent based on Abnormal Involuntary Movements Scale (AIMS) scores. haplotype generated by markers and rs2701124 also and, after adjustment...
Abstract Parkinson’s disease (PD) is a complex neurodegenerative disorder without cure. The onset of PD symptoms corresponds to 50% loss midbrain dopaminergic (mDA) neurons, limiting early-stage understanding PD. To shed light on early development, we study time series scRNA-seq datasets mDA neurons obtained from patient-derived induced pluripotent stem cell differentiation. We develop new data integration method based Non-negative Matrix Tri-Factorization that integrates these with...
Mutations in PINK1 and Parkin are two of the main causes recessive early-onset Parkinson's disease (PD). We generated human induced pluripotent stem cells (hiPSCs) from fibroblasts a 64-year-old male patient with homozygous ILE368ASN mutation PINK1, who experienced onset at 33 years, 61-year-old female heterozygous for R275W Parkin, 44 years. Array comparative genomic hybridization (aCGH) determined genotypic variation each line. The cell lines were successfully used to generate midbrain...
The cerebral frontal cortex of schizophrenia patients shows elevated levels RNA for calcium/calmodulin‐dependent protein kinase II beta (CaMKIIβ). In addition, recent research that animal models consistently show dopamine 2 receptors in their high‐affinity state (D2High), the major target antipsychotic medication. present study was done to examine whether an alteration CaMKIIβ, respect CaMKIIα, could lead altered D2High receptors. We used quantitative real‐time PCR measure CaMKIIα and...
Abstract Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, characterized by loss of dopaminergic neurons (mDA) in midbrain. The heterogenous pathology and complex underlying mechanisms are only partly understood there no treatment able to reverse PD progression. Here, we targeted focusing on ILE368ASN mutation within PINK1 (PARK6) gene systematically midbrain obtained from human induced pluripotent stem cells (iPSCs). Single-cell RNA sequencing (RNAseq)...