A5073734321- Ion channel regulation and function
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Adenosine and Purinergic Signaling
- Alzheimer's disease research and treatments
- Neurogenesis and neuroplasticity mechanisms
- Nuclear Receptors and Signaling
- Muscle Physiology and Disorders
- Cellular transport and secretion
- Immune cells in cancer
- Neuroscience of respiration and sleep
- Parkinson's Disease Mechanisms and Treatments
- Erythrocyte Function and Pathophysiology
- Cellular Mechanics and Interactions
- Lipid Membrane Structure and Behavior
- Amyotrophic Lateral Sclerosis Research
- Cell Adhesion Molecules Research
- Nerve injury and regeneration
- Vagus Nerve Stimulation Research
- Stress Responses and Cortisol
- Cardiovascular Effects of Exercise
- Myasthenia Gravis and Thymoma
- Neurological diseases and metabolism
- Biochemical and Structural Characterization
- Cholinesterase and Neurodegenerative Diseases
University of Eastern Finland
2015-2025
Finland University
2010-2025
Kuopio University Hospital
2020
Institute for Molecular Science
2020
Kazan Federal University
2015-2019
Kazan Institute of Biochemistry and Biophysics
2002-2017
Johannes Gutenberg University Mainz
2017
University Medical Center of the Johannes Gutenberg University Mainz
2017
University of Padua
2017
University of Turku
2017
Alzheimer's disease (AD) is a common neurodegenerative disorder and the leading cause of cognitive impairment. Due to insufficient understanding mechanisms, there are no efficient therapies for AD. Most studies have focused on neuronal cells, but astrocytes also been suggested contribute AD pathology. We describe here generation functional from induced pluripotent stem cells (iPSCs) derived patients with PSEN1 ΔE9 mutation, as well healthy gene-corrected isogenic controls. manifest hallmarks...
Here we elucidate the effect of Alzheimer disease (AD)-predisposing genetic backgrounds, APOE4, PSEN1ΔE9, and APPswe, on functionality human microglia-like cells (iMGLs). We present a physiologically relevant high-yield protocol for producing iMGLs from induced pluripotent stem cells. Differentiation is directed with small molecules through primitive erythromyeloid progenitors to re-create microglial ontogeny yolk sac. The express signature genes respond ADP intracellular Ca2+ release...
Abstract In Parkinson`s disease (PD), the loss of dopaminergic (DA) neurons in substantia nigra pars compacta is associated with Lewy bodies arising from accumulation alpha-synuclein protein which leads ultimately to movement impairment. While PD has been considered a DA neurons, glial contribution, particular that astrocytes, pathogenesis starting be uncovered. Here, we report findings astrocytes derived induced pluripotent stem cells LRRK2 G2019S mutant patients, one patient also carrying...
Microglia are the endogenous immune cells of brain and act as sensors pathology to maintain homeostasis eliminate potential threats. In Alzheimer's disease (AD), toxic amyloid beta (Aβ) accumulates in forms stiff plaques. late-onset AD accounting for 95% all cases, this is thought be due reduced clearance Aβ. Human genome-wide association studies animal models suggest that results from aberrant function microglia. While impact neurochemical pathways on microglia had been broadly studied,...
The mechanisms controlling pain in newborns during delivery are poorly understood. We explored the hypothesis that oxytocin, an essential hormone for labor and a powerful neuromodulator, exerts analgesic actions on delivery. Using thermal tail-flick assay, we report sensitivity is two-fold lower rat pups immediately after birth than 2 days later. Oxytocin receptor antagonists strongly enhanced newborn, but not 2-day-old rats, whereas oxytocin reduced at both ages suggesting endogenous...
Human cerebral organoids, derived from induced pluripotent stem cells, offer a unique in vitro research window to the development of cortex. However, key player developing brain, microglia, do not natively emerge organoids. Here we show that erythromyeloid progenitors (EMPs), differentiated migrate and mature into microglia-like cells interact with synaptic material. Patch-clamp electrophysiological recordings population supported emergence more diversified neuronal phenotypes displaying...
Formation, maturation, stabilization, and functional efficacy of the neuromuscular junction (NMJ) are orchestrated by transsynaptic autocrine signals embedded within synaptic cleft. Here, we demonstrate that collagen XIII, a nonfibrillar transmembrane collagen, is another such signal. We show XIII expressed muscle its ectodomain can be proteolytically shed into extracellular matrix. The protein was found present in postsynaptic membrane basement membrane. To identify role for at NMJ, mice...
Recent studies suggested contribution of homocysteine (HCY) to neurodegenerative disorders and migraine. However, HCY effect in the nociceptive system is essentially unknown. To explore mechanism action, we studied short- long-term effects this amino acid on rat peripheral central neurons. induced intracellular Ca²⁺ transients cultured trigeminal neurons satellite glial cells (SGC), which were blocked by NMDA antagonist AP-5 neurons, but not SGCs. In contrast,...
Reactive oxygen species (ROS) participate in various physiological and pathological processes the nervous system, but specific pathways that mediate ROS signalling remain largely unknown. Using electrophysiological techniques biochemical evaluation of isolated fusion proteins, we explored sensitivity to standard oxidative stress entire synapse, pre-synaptic machinery essential proteins underlying transmitter exocytosis. Oxidative induced by H(2)O(2) plus Fe(2+) inhibited both evoked...
Both transmembrane and extracellular cues, one of which is collagen XIII, regulate the formation function neuromuscular synapse, their absence results in myasthenia. We show that phenotypical changes XIII knock-out mice are milder than symptoms human patients, but Col13a1-/- recapitulate major muscle findings congenital myasthenic syndrome type 19 serve as a disease model. In lack synapses do not reach full size, alignment, complexity resulting reduced strength. Collagen particularly...
Studies of neuronal functions during the pathological progression Alzheimers disease (AD) in humans are limited due to lack live human brain tissue from patients with AD. To address this gap, we have established an exceptional approach study electrophysiological properties and cell morphologies neurons acute slices obtained cortical biopsies idiopathic normal pressure hydrocephalus (iNPH). Histological examination Broadman area 8-9 these revealed that approximately 40% show signs early...
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motoneurons which progresses differentially in males and females for unknown reason. Here we measured gender differences pre- postsynaptic parameters the neuromuscular transmission mutant G93A-SOD1 mouse model ALS. Using intracellular microelectrode technique recorded miniature evoked endplate potentials (MEPPs EPPs) diaphragm muscle mice at early symptomatic stage. While no evident alterations amplitude MEPPs was observed...
LRRK2-G2019S is one of the most common Parkinson's disease (PD)-associated mutations and has been shown to alter microglial functionality. However, impact on transcriptional profile human induced pluripotent stem cell-derived microglia-like cells (iMGLs) how it corresponds microglia in idiopathic PD brain not known. Here we demonstrate that carrying iMGL recapitulate aspects signature midbrain microglia. subtle donor-dependent alterations mitochondrial respiration, phagocytosis cytokine...
Generation of supramolecular architectures through controlled linking suitable building blocks can offer new perspectives to medicine and applied technologies. Current strategies often rely on chemical methods that have limitations cannot take full advantage the recombinant Here we used SNARE proteins, namely, syntaxin, SNAP25, synaptobrevin, which form stable tetrahelical complexes drive fusion intracellular membranes, as versatile tags for irreversible synthetic functional units. We show...
Homocysteine (HCY) is a pro-inflammatory sulphur-containing redox active endogenous amino acid, which concentration increases in neurodegenerative disorders including amyotrophic lateral sclerosis (ALS). A widely held view suggests that HCY could contribute to neurodegeneration via promotion of oxidative stress. However, the action on motor nerve terminals has not been investigated so far. We previously reported stress inhibited synaptic transmission at neuromuscular junction, targeting...
Abstract Corelease of ATP with ACh from motor endings suggests a physiological role for in synaptic transmission. We previously showed that, on skeletal muscle, directly inhibited release via presynaptic P2 receptors. The receptor identification (P2X or P2Y) and its transduction mechanism remained, however, unknown. In the present study using voltage‐clamp technique we analyzed properties receptors subsequent effector mechanisms. adenosine presynaptically depressed multiquantal end‐plate...
The m.3243A>G mutation in mitochondrial tRNA-Leu(UUR) is one of the most common pathogenic DNA mutations humans. clinical manifestations are highly heterogenous and causes for drastic variability unknown. Approximately third patients suffer from cardiac disease, which often increases mortality. Why only some develop cardiomyopathy Here, we studied molecular effects a high load on cardiomyocyte functionality, using cells derived induced pluripotent stem (iPSC-CM) two different patients,...
Abstract We have shown previously that ATP inhibits transmitter release at the neuromuscular junction through action on metabotropic P2Y receptors coupled to specific second messenger cascades. In present study we recorded K + or Ca 2+ currents in motor nerve endings blocked channels order explore nature of downstream presynaptic effectors. Endplate were presynaptically depressed by ATP. Blockers ‐activated ‐channels, such as iberiotoxin, apamin tetraethylammonium, did not change depressant...
Pain is the most unbearable symptom accompanying primary bone cancers and metastases. Bone resorptive disorders are often associated with hypercalcemia, contributing to pathologic process. Nitrogen-containing bisphosphonates (NBPs) efficiently used treat Apart from their toxic effect on cancer cells, NBPs also provide analgesia via poorly understood mechanisms. We previously showed that NBPs, by inhibiting mevalonate pathway, induced formation of novel ATP analogs such as ApppI...
Transmembrane collagen XIII has been linked to maturation of the musculoskeletal system. Its absence in mice (Col13a1-/- ) results impaired neuromuscular junction (NMJ) differentiation and function, while transgenic overexpression (Col13a1oe leads abnormally high bone mass. Similarly, loss-of-function mutations COL13A1 humans produce muscle weakness, decreased motor synapse function mild dysmorphic skeletal features. Here, analysis exogenous various muscles revealed highly increased...
Functional interactions between presynaptic adenosine and acetylcholine (ACh) autoreceptors were studied at the frog neuromuscular junction by recording miniature end-plate potentials (MEPPs) during bath or local application of agonists. The frequency MEPPs was reduced acting on A1 receptors (EC(50) = 1.1 microm) carbachol muscarinic M2 1.8 microm). However, did not produce depressant effect when it applied after action had reached its maximum. This phenomenon implied that negative...
Abstract Human stem cell-derived brain organoids provide a physiologically relevant in vitro 3D model for studies of neurological development that are unique to the human nervous system. Prior have reported protocols support maturation microglia from mesodermal progenitors leading innately developing within organoids. However, although known neuronal rodents, none previous what is impact on growth and Here we show incorporating microglial into organoid supports maturation, emergence neurons...