A5019552841- Nerve injury and regeneration
- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Nuclear Receptors and Signaling
- Memory and Neural Mechanisms
- Neurotransmitter Receptor Influence on Behavior
- Neurogenesis and neuroplasticity mechanisms
- Autism Spectrum Disorder Research
- CRISPR and Genetic Engineering
- Receptor Mechanisms and Signaling
- Alzheimer's disease research and treatments
- Sleep and Wakefulness Research
- Adenosine and Purinergic Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Sleep and related disorders
- Neural dynamics and brain function
- Pancreatic function and diabetes
- Amino Acid Enzymes and Metabolism
- Attention Deficit Hyperactivity Disorder
- Cellular transport and secretion
- Neurological disorders and treatments
- Neuroscience and Neural Engineering
- Adipose Tissue and Metabolism
- RNA Research and Splicing
- Restless Legs Syndrome Research
University of Helsinki
2011-2023
Helsinki Institute of Physics
2022
Czech Academy of Sciences, Institute of Biotechnology
2014-2017
Degeneration of nigrostriatal dopaminergic system is the principal lesion in Parkinson's disease. Because glial cell line-derived neurotrophic factor (GDNF) promotes survival dopamine neurons vitro and vivo, intracranial delivery GDNF has been attempted for disease treatment but with variable success. For improving GDNF-based therapies, knowledge on physiological role endogenous at sites its expression important. However, due to limitations existing genetic model systems, such scarce. Here,...
Parkinson's disease (PD) is a neurodegenerative disorder with significant immune component, as demonstrated by changes in biomarkers patients' biofluids. However, which specific cells are responsible for those unclear because most can be produced various cell types.The aim of this study was to explore monocyte involvement PD.We investigated the monocyte-specific biomarker sCD163, soluble form receptor CD163, cerebrospinal fluid (CSF) and serum two experiments, compared it other clinical...
A molecular hallmark in Parkinson's disease (PD) pathogenesis are α-synuclein aggregates. Cerebral dopamine neurotrophic factor (CDNF) is an atypical growth that mostly resident the endoplasmic reticulum but exerts its effects both intracellularly and extracellularly. One of beneficial CDNF can be protecting neurons from toxic α-synuclein. Here, we investigated on aggregation vitro vivo. We found directly interacts with a KD = 23 ± 6 nM reduces auto-association. Using nuclear magnetic...
Abstract Presynaptic increase in striatal dopamine is the primary dopaminergic abnormality schizophrenia, but underlying mechanisms are not understood. Here, we hypothesized that increased expression of endogenous GDNF could induce abnormalities resemble those seen schizophrenia. To test impact elevation, without inducing adverse effects caused by ectopic overexpression, developed a novel vivo approach to conditionally expression. We found 2–3-fold brain was sufficient molecular, cellular,...
Cerebral dopamine neurotrophic factor (CDNF) is neuroprotective for nigrostriatal neurons and restores dopaminergic function in animal models of Parkinson's disease (PD). To understand the role CDNF mammals, we generated knockout mice (Cdnf-/-), which are viable, fertile, have a normal life-span. Surprisingly, an age-dependent loss enteric occurs selectively submucosal but not myenteric plexus. This neuronal consequence increased apoptosis neurodegeneration autophagy. Quantitatively,...
ABSTRACT Background Parkinson's disease (PD) is associated with proteostasis disturbances and accumulation of misfolded α‐synuclein (α‐syn), a cytosolic protein present in high concentrations at pre‐synaptic neuronal terminals. It primary constituent intracellular aggregates known as Lewy neurites or bodies. Progression pathology caused by the prion‐like self‐templating properties α‐syn characteristic feature brains PD patients. Glial cell line‐derived neurotrophic factor (GDNF) promotes...
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 subunit-deficient (GluA1-/-) mice display novelty-induced hyperactivity, cognitive and social defects may model psychiatric disorders, such as schizophrenia depression/mania. We used c-Fos expression in GluA1-/- to identify brain regions responsible for hyperlocomotion. Exposure a novel cage 2 h significantly increased many both wild-type knockout mice. Interestingly, the clearest genotype effect was observed...
Dopamine neurons of the ventral tegmental area (VTA) are involved at early phases drug addiction. Even first in vivo dose various abused drugs induces glutamate receptor plasticity excitatory synapses these neurons. Benzodiazepines that suppress inhibitory GABAergic interneurons VTA via facilitation synaptic GABA A receptors have induced neuroplasticity dopamine due to this disinhibitory mechanism. Here, we tested a non-benzodiazepine direct site agonist 4,5,6,7-tetrahydroisoxazolol[4,5- c...
Midbrain dopamine neuron dysfunction contributes to various psychiatric and neurological diseases, including drug addiction Parkinson's disease. Because of its well established dopaminotrophic effects, the therapeutic potential glial cell line-derived neurotrophic factor (GDNF) has been studied extensively in disorders with disturbed homeostasis. However, outcomes from preclinical clinical studies vary, highlighting a need for better understanding physiological role GDNF on striatal...
GABAA receptors are the main fast inhibitory neurotransmitter in mammalian brain, and targets for many clinically important drugs widely used treatment of anxiety disorders, insomnia anesthesia. Nonetheless, there significant risks associated with long-term use these particularly related to development tolerance addiction. Addictive mechanisms receptor poorly known, but recent findings suggest that those may induce aberrant neuroadaptations brain reward circuitry. Recently, benzodiazepines,...
Abstract The neural circuits regulating motivation and movement include midbrain dopaminergic neurons associated inhibitory GABAergic excitatory glutamatergic in the anterior brainstem. Differentiation of specific subtypes mouse embryonic brainstem is controlled by a transcription factor Tal1 . This study characterizes behavioral neurochemical changes caused absence function. cko mutant mice are hyperactive, impulsive, hypersensitive to reward, have learning deficits habituation defect novel...
In state-dependency, information retrieval is most efficient when the animal in same state as it was during acquisition. State-dependency has been implicated a variety of learning and memory processes, but its mechanisms remain to be resolved. Here, mice deficient AMPA-type glutamate receptor GluA1 subunits were first conditioned morphine (10 or 20 mg/kg s.c. eight sessions over four days) using an unbiased procedure, followed by testing for place preference at states that different from one...
Abstract The existent pre‐clinical models of Parkinson's disease do not simultaneously recapitulate severe degeneration dopamine neurons and the occurrence alpha‐synuclein (aSyn) aggregation in one study system. In this study, we injected aSyn pre‐formed fibrils (PFF) 6‐hydroxydopamine (6‐OHDA) unilaterally into striatum C57BL/6 wild‐type male mice at an interval 2 weeks to induce protein trigger loss model studied behavioural effects combination these mice. 6‐OHDA was tested three different...
Abstract Neurodegenerative diseases are associated with proteostasis disturbances and accumulation of fibrillar proteins into insoluble aggregates. Progressive age-related degeneration dopamine neurons is a primary cause motor dysfunctions in Parkinson’s disease (PD) substantial evidence supports critical involvement α-synuclein (α-syn) the etiology PD. α-syn cytosolic protein present high concentrations pre-synaptic neuronal terminals constituent intracellular aggregates known as Lewy...
Parkinson's disease (PD) is characterized by the loss of nigrostriatal dopamine (DA) neurons and presence alpha-synuclein (αSyn)-positive Lewy body (LB) pathology. In this study, we attempted to recapitulate both these features in a novel vitro model for PD. To achieve this, combined αSyn pre-formed fibril (PFF)-seeded LB-like pathology with 6-hydroxydopamine (6-OHDA)-induced mitochondrial toxicity mouse embryonic midbrain cultures. pilot therapeutics testing, assessed effects cerebral...
Abstract Currently available genetic tools do not allow researchers to upregulate (‘Knock Up’) the levels of a given protein while retaining its cell-type-specific regulation. As result, we have limited ability develop overexpression-related disease models, study contribution single genes in diseases caused by copy number variations and identify pathways for drug targets. Here two approaches endogenous gene upregulation: c onditional K nock U p (cKU) utilizing Cre/lox system, CRISPR-Cas9...
THIP (gaboxadol), a superagonist of the delta subunit-containing extrasynaptic GABAA receptors, produces persistent neuroplasticity in dopamine (DA) neurons ventral tegmental area (VTA), similarly to rewarding drugs abuse. However, unlike them lacks abuse potential and induces conditioned place aversion mice. The mechanism underlying aversive effects remains elusive. Here, we show that mild were detected 2 hours after administration likely reflecting an anxiety-like state with increased...
ABSTRACT Parkinson’s disease is a neurodegenerative disorder with significant immune component. Numerous studies have reported alterations on biomarkers in CSF and serum that associate symptoms PD patients. However, it unclear, which specific cells are responsible for the changes those biomarkers; since most of these cytokines or chemokines, can be produced by variety cells, even neurons glia brain. Here, we investigate monocyte/macrophage-specific biomarker: sCD163, soluble form receptor...