A5086623048- Erythrocyte Function and Pathophysiology
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Pain Mechanisms and Treatments
- Receptor Mechanisms and Signaling
- Chemical and Physical Studies
- Ion Channels and Receptors
- Neurogenesis and neuroplasticity mechanisms
- Signaling Pathways in Disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Peptidase Inhibition and Analysis
- Protease and Inhibitor Mechanisms
- Venomous Animal Envenomation and Studies
- Neuroscience and Neural Engineering
- Biological and pharmacological studies of plants
- Mitochondrial Function and Pathology
- Hearing, Cochlea, Tinnitus, Genetics
- Treatment of Major Depression
- Pain Management and Placebo Effect
- S100 Proteins and Annexins
- Axon Guidance and Neuronal Signaling
- Medicinal Plants and Neuroprotection
- Neural dynamics and brain function
- Circadian rhythm and melatonin
- Photochromic and Fluorescence Chemistry
Linköping University
2021-2025
National Center for Complementary and Integrative Health
2016-2022
National Institutes of Health
2017-2021
Wroclaw Medical University
2010-2015
The senses of touch and proprioception evoke a range perceptions rely on the ability to detect transduce mechanical force. molecular neural mechanisms underlying these sensory functions remain poorly defined. stretch-gated ion channel PIEZO2 has been shown be essential for aspects mechanosensation in model organisms.We performed whole-exome sequencing analysis two patients who had unique neuromuscular skeletal symptoms, including progressive scoliosis, that did not conform standard...
The stretch-gated ion channel PIEZO2 is required for inflammation-induced tactile allodynia.
An increasing body of data has shown that matrix metalloproteinase-9 (MMP-9), an extracellularly acting, Zn2+-dependent endopeptidase, is important not only for pathologies the central nervous system but also neuronal plasticity. Here, we use three independent experimental models to show enzymatic activity MMP-9 causes elongation and thinning dendritic spines in hippocampal neurons. These are: a recently developed transgenic rat overexpressing autoactivating MMP-9, dissociated cultures,...
Piezo2 is a mechanically activated ion channel required for touch discrimination, vibration detection, and proprioception. Here, we discovered that extensively spliced, producing different isoforms with distinct properties. Sensory neurons from both mice humans express large repertoire of variants, whereas non-neuronal tissues predominantly single isoform. Notably, even within sensory ganglia, demonstrate the splicing to be cell type specific. Biophysical characterization revealed...
Efficient and homogeneous in vitro generation of peripheral sensory neurons may provide a framework for novel drug screening platforms disease models touch pain. We discover that, by overexpressing NGN2 BRN3A, human pluripotent stem cells can be transcriptionally programmed to differentiate into surprisingly uniform culture cold- mechano-sensing neurons. Although such neuronal subtype is not found mice, we identify molecular evidence its existence ganglia. Combining BRN3A programming with...
beta-Catenin, together with LEF1/TCF transcription factors, activates genes involved in the proliferation and differentiation of neuronal precursor cells. In mature neurons, beta-catenin participates dendritogenesis synaptic function as a component cadherin cell adhesion complex. However, transcriptional activity these cells remains elusive. present study, we found that adult mouse brain, LEF1 accumulate nuclei neurons specifically thalamus. The particular electrophysiological properties...
Abstract The sensation of pressure allows us to feel sustained compression and body strain. While our understanding cutaneous touch has grown significantly in recent years, how deep tissue sensations are detected remains less clear. Here, we use quantitative sensory evaluations patients with rare disorders, as well nerve blocks typical individuals, probe the neural genetic mechanisms for detecting non-painful pressure. We show that ability perceive innocuous pressures is lost when myelinated...
Primary afferent neurons that convey somatosensory modalities comprise two large, heterogeneous populations: small-diameter give rise to slowly conducting unmyelinated axonal C fibers and medium-to-large diameter with fast myelinated A fibers. Despite these major groupings, tools differentiate between primary by genetic targeting have not been available; in particular, whereas numerous mouse driver lines exist target different fiber populations, populations are scarce. Here we describe a...
Spinal nociceptive withdrawal reflexes are widely believed to rely on unmyelinated and thinly myelinated fibers that also signal affective motivational aspects of pain. Here we discover a population mechanoreceptive nociceptor forms free nerve endings as well circumferential around hair follicles, exclusively terminate in the deep spinal dorsal horn. Optogenetic activation these triggers rapid precise selective for targeted limb, while silencing increases threshold mechanical reflexes. By...
Abstract Primary afferent neurons that convey somatosensory modalities comprise two large, heterogeneous populations: small-diameter give rise to slowly conducting unmyelinated axonal C fibers and medium-to-large diameter with fast myelinated A fibers. Despite these major groupings, tools differentiate between primary by genetic targeting have not been available; in particular, whereas numerous mouse driver lines exist target different fiber populations, populations are scarce. Here we...
GABA receptors (GABA A Rs) mediate inhibition in the adult brain. These channels are heteropentamers and their ligand binding sites localized at β(+)/α(−) interfaces. As expected, mutations of binding-site residues affect kinetics but accumulating evidence indicates that gating is also altered, although underlying mechanisms unclear. We investigated impact hydrophobic box residue α 1 (−), F64 (α F64), on rat recombinant β γ 2 receptors. The analysis current responses to rapid agonist...
α-Thujone (1a), a constituent of wormwood, has been suspected to cause adverse psychoactive reactions in addicted drinkers absinthe. While the content 1a absinthe is too low for such effects, at higher doses it can indeed induce seizures and inhibit GABA(A) receptors (GABA(A)Rs). The effect on GABAergic synaptic currents mechanisms by which modulates GABA(A)Rs remain unknown. To address these issues, cultured hippocampal neurons were used investigate action miniature inhibitory postsynaptic...
The PIEZO2 ion channel is critical for transducing light touch into neural signals but not considered necessary acute pain in humans. Here, we discovered an exception – a form of mechanical evoked by hair pulling. Based on observations rare group individuals with deficiency syndrome, demonstrated that hair‐pull dependent transduction. Studies control participants showed triggered distinct nocifensive response, including nociceptive reflex. Observations Aβ deafferented and nerve conduction...
Somatosensation, the detection and transduction of external internal stimuli such as temperature or mechanical force, is vital to sustaining our bodily integrity. But still, some mechanisms distinct are not entirely understood, especially when noxious perception turns into chronic pain. Over past decade major progress has increased understanding in areas mechanotransduction sensory neuron classification. However, it particular access human pluripotent stem cells possibility generating...
Background and purpose: Oenanthotoxin (OETX), a polyacetylenic alcohol from plants of the genus Oenanthe , has recently been identified as potent inhibitor GABA‐evoked currents. However, effects OETX on inhibitory postsynaptic currents (IPSCs), well pharmacological mechanism(s) underlying its GABA A receptors, remain unknown. The purpose this study was to elucidate mechanism inhibition GABAergic by OETX. Experimental approach: Effects were studied using patch clamp technique rat cultured...
Summary The PIEZO2 ion channel is critical for transducing light touch into neural signals but not considered necessary acute pain in humans. Here, we discovered an exception – a form of mechanical evoked by hair pulling. Based on observations rare group individuals with deficiency syndrome, demonstrated that hair-pull dependent transduction. Studies control participants showed triggered distinct nocifensive response, including nociceptive reflex. Observations Aβ deafferented and nerve...
Abstract Somatosensation, the detection and transduction of external internal stimuli, has fascinated scientists for centuries. But still, some mechanisms how distinct stimuli are detected transduced not entirely understood. Over past decade major progress increased our understanding in areas such as mechanotransduction or sensory neuron classification. Additionally, accessibility to human pluripotent stem cells possibility generate study neurons enriched somatosensory research field. Based...
An increasing body of data has shown that matrix metalloproteinase-9 (MMP-9), an extracellularly acting, Zn2+-dependent endopeptidase, is important not only for pathologies the central nervous system but also neuronal plasticity. Here, we use three independent experimental models to show enzymatic activity MMP-9 causes elongation and thinning dendritic spines in hippocampal neurons. These are: a recently developed transgenic rat overexpressing autoactivating MMP-9, dissociated cultures,...
<title>Abstract</title> The diversity of mechanical pain sensations in humans cannot be explained based on our current understanding pain-sensing neural classes the skin. To begin to bridge this gap, we dissected basis a distinct form sensation evoked by hair pulling humans. Based observations rare group individuals with PIEZO2 deficiency syndrome, demonstrated that hair-pull is dependent transduction. Single-unit axonal recordings revealed specific class cooling-responsive, rapidly...