- Receptor Mechanisms and Signaling
- Endoplasmic Reticulum Stress and Disease
- Genetics and Neurodevelopmental Disorders
- Adenosine and Purinergic Signaling
- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Pancreatic function and diabetes
- Pharmacological Receptor Mechanisms and Effects
- Neuropeptides and Animal Physiology
- RNA regulation and disease
- Pharmacological Effects and Toxicity Studies
- Adipose Tissue and Metabolism
- Liver Disease Diagnosis and Treatment
- Chemical Synthesis and Analysis
- Diet and metabolism studies
- Genomics, phytochemicals, and oxidative stress
- Endometrial and Cervical Cancer Treatments
- Nerve injury and regeneration
- Epigenetics and DNA Methylation
- Nuclear Receptors and Signaling
- Endometriosis Research and Treatment
- Biochemical effects in animals
- Bipolar Disorder and Treatment
- Reproductive System and Pregnancy
National Institute of Chemical Physics and Biophysics
2021-2025
University of Tartu
2011-2021
Czech Academy of Sciences, Institute of Physiology
2011
Center for Translational Molecular Medicine
2011
National Institutes of Health
2006-2010
National Institute on Alcohol Abuse and Alcoholism
2006-2008
Karolinska Institutet
1999-2006
University of Iowa
2006
University of California, Los Angeles
2006
Alzheimer’s Disease Neuroimaging Initiative
2006
Antagonistic and reciprocal interactions are known to exist between adenosine dopamine receptors in the striatum. In present study, double immunofluorescence experiments with confocal laser microscopy showed a high degree of colocalization A(2A) (A(2A)R) D(2) (D(2)R) cell membranes SH-SY5Y human neuroblastoma cells stably transfected D(2)R cultured striatal cells. A(2A)R/D(2)R heteromeric complexes were demonstrated coimmunoprecipitation membrane preparations from D(2)R-transfected mouse...
Alcoholism is a chronic relapsing disorder with substantial heritability. Uncovering gene-environment interactions underlying this disease process can aid identification of novel treatment targets. Here, we found lowered threshold for stress-induced reinstatement alcohol seeking in Marchigian-Sardinian Preferring (msP) rats genetically selected high preference. In situ hybridization panel 20 stress-related genes 16 brain regions was used to screen differential gene expression that may...
Current therapeutics of endometriosis focus on hormonal disruption endometriotic lesions (ectopic endometrium, EcE). Recent findings show higher glycolysis utilization in EcE, suggesting non-hormonal strategy for disease treatment that addresses cellular metabolism. Identifying metabolically altered cell types EcE is important targeted metabolic drug therapy without affecting eutopic endometrium (EuE). Here, using single-cell RNA-sequencing, we examine twelve pathways paired samples EuE and...
Abstract Wolfram syndrome (WS) is a rare autosomal-recessive disorder that caused by mutations in the WFS1 gene and characterized juvenile-onset diabetes, optic atrophy, hearing loss number of other complications. Here, we describe creation phenotype Wfs1 mutant rats, which exon 5 deleted, resulting 27 amino acids from protein sequence. These Wfs1-ex5-KO232 rats show progressive glucose intolerance, culminates development diabetes mellitus, glycosuria, hyperglycaemia severe body weight 12...
Cell models play a central role in preclinical research aimed at the mechanism of disease and drug discovery. The outside environment cells, including levels nutrients oxygen tension, regulates cellular stress response pathways. Routinely used vitro often overlook cell growth conditions. This study to evaluate effect substituting classic media (DMEM) with matching nutrient composition human plasma (Plasmax) on viability, activation nuclear factor erythroid 2-related 2 (Nrf2), glutathione...
Wolfram syndrome (WS) is a rare autosomal recessive disorder caused by mutations in the WFS1 (Wolframin1) gene. The first manifests as diabetes mellitus, followed optic nerve atrophy, deafness, and neurodegeneration. underlying mechanism believed to be dysregulation of endoplasmic reticulum (ER) stress response, which ultimately leads cellular death. Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists has been shown normalize ER response several vitro vivo models. Early chronic...
Wolfram syndrome (WS) is a rare neurodegenerative disorder that mainly characterized by diabetes mellitus, optic nerve atrophy, deafness, and progressive brainstem degeneration. Treatment with GLP-1 receptor agonists has shown promising anti-diabetic effect in WS treatment both animal models human patients. Since previous research tended to focus on investigation of the first symptom, aim present study was examine liraglutide WS-associated neurodegeneration. We took 9-month-old Wfs1...
Wolfram syndrome (WS) is a monogenic progressive neurodegenerative disease and characterized by various neurological symptoms, such as optic nerve atrophy, loss of vision, cognitive decline, memory impairment, learning difficulties. GLP1 receptor agonist liraglutide BDNF mimetic 7,8-dihydroxyflavone (7,8-DHF) have had protective effect to visual pathway in different rat models disorders. Although synergistic co-treatment has not been reported before therefore the aim current study was...
The aim of present study was to describe changes in gene expression the temporal lobe mice induced by deletion Wfs1 gene. Temporal lobes samples were analyzed using Affymetrix Mouse Genome 420 2 GeneChips and profiles functionally annotated with GSEA Ingenuity Pathway Analysis. We found that mutant are significantly smaller (20.9 +/- 1.6 g) than their wild-type counterparts (31.0 0.6 g, P < 0.0001). This difference existed 129S6 C57B6 backgrounds. Interestingly, microarray analysis...
Wolfram syndrome (WS), also known as a DIDMOAD (diabetes insipidus, early-onset diabetes mellitus, optic nerve atrophy and deafness) is rare autosomal disorder caused by mutations in the Wolframin1 (WFS1) gene. Previous studies have revealed that glucagon-like peptide-1 receptor agonist (GLP1 RA) are effective delaying restoring blood glucose control WS animal models patients. The GLP1 RA liraglutide has been shown to neuroprotective properties aged rats. an early-onset, chronic condition....
Beta-arrestin 2 is a multifunctional key component of the G protein-coupled receptor complex and involved in mu-opiate dopamine D2 signaling, both which are thought to mediate rewarding effects ethanol consumption. We identified elevated expression beta-arrestin gene (Arrb2) striatum hippocampus ethanol-preferring AA rats compared their nonpreferring counterpart ANA line. Differential mRNA was accompanied by different levels Arrb2 protein. The associated with 7-marker haplotype complete...
Abstract: Analysis of the biochemical differences in energy metabolism among bi-dimensional (2D) and tri-dimensional (3D) cultured cancer cell models actual human tumors was undertaken. In 2D cells, oxidative phosphorylation (OxPhos) fluxes range is 2.5-19 nmol O2/min/mg cellular protein. Hypoxia drastically decreased OxPhos flux by 2-3 times models, similar to what occurs mature multicellular tumor spheroids (MCTS), a representative 3D model. However, mitochondrial protein contents enzyme...
ABSTRACT The reinforcing properties of ethanol are in part attributed to interactions between opioid and dopaminergic signaling pathways, but intracellular mediators such poorly understood. Here we report that an acute challenge induces a robust phosphorylation two key signal transduction kinases, AKT DARPP‐32, the striatum mice. Ethanol‐induced was blocked by receptor antagonist naltrexone unaffected blockade dopamine D2 receptors via sulpiride. In contrast, DARPP‐32 abolished both...