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Publications (87)
Spinal cord injury (SCI) is a condition that affects between 8.8 and 246 people in a million and, unlike many other neurological disorders, it affects mostly young people, causing deficits in sensory, motor, and autonomic functions. Promoting the regrowth of axons is one of the most important goals for the neurological recovery of patients after SC...
Spinal cord injury (SCI) is a condition that affects between 8.8 and 246 people in a million and, unlike many other neurological disorders, it affects mostly young people, causing deficits in sensory, motor, and autonomic functions. Promoting regrowth of axons is one of the most important goals for the neurological recovery of patients after SCI, b...
This review discusses the experimental findings of several recent studies which investigated the functional role of AMPA receptors (AMPARs) in oligodendrocyte lineage cells in vivo, in mice and in zebrafish. These studies provided valuable information showing that oligodendroglial AMPARs may be involved in the modulation of proliferation, different...
Receptors for α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPARs) are ligand‐gated ionotropic receptors for glutamate that is a major excitatory neurotransmitter in the central nervous system. AMPARs are located at postsynaptic sites of neuronal synapses where they mediate fast synaptic signaling and synaptic plasticity. Remarkably, AMPAR...
Despite significant advances in our understanding of the pathophysiology of multiple sclerosis (MS), knowledge about contribution of individual ion channels to axonal impairment and remyelination failure in progressive MS remains incomplete. Ion channel families play a fundamental role in maintaining white matter (WM) integrity and in regulating WM...
In the peripheral nervous system, the vast majority of axons are accommodated within the fibre bundles that constitute the peripheral nerves. Axons within the nerves are in close contact with myelinating glia, the Schwann cells that are ideally placed to respond to, and possibly shape, axonal activity. The mechanisms of intercellular communication...
Fast chemical synaptic transmission is a major form of neuronal communication in the nervous system of mammals. Another important, but very different, form of intercellular communication is volume transmission, which is a slower non‐synaptic signaling. The amino acid glutamate is the most abundant excitatory neurotransmitter in the nervous system,...
The functional role of AMPA receptor (AMPAR)-mediated synaptic signaling between neurons and oligodendrocyte precursor cells (OPCs) remains enigmatic. We modified the properties of AMPARs at axon-OPC synapses in the mouse corpus callosum in vivo during the peak of myelination by targeting the GluA2 subunit. Expression of the unedited (Ca²⁺ permeabl...
Schwann cells (SCs) are myelinating cells of the PNS. Although SCs are known to express different channels and receptors on their surface, little is known about the activation and function of these proteins. Ionotropic glutamate receptors are thought to play an essential role during development of SC lineage and during peripheral nerve injury, so w...
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Oligodendrocytes are glial cells of the central nervous system. One of their major tasks is to enwrap neuronal axons with myelin, providing electrical insulation of axons and a dramatic increase in the speed of nerve impulse propagation. Oligodendrocytes develop from oligodendrocyte precursor cells (OPCs). Self-renewal of OPCs, their...
Effect of electrical stimulation on the number and differentiation of OPCs three days after the stimulation session.
(A-B) Average density of (A)OPCs and (B)pre-OLs in corpus callosum upon electrical stimulation of callosal axons at 25 Hz (n = 3 mice, total 11slices) or 300 Hz (n = 3 mice, total 10 slices), vs. sham-treated control animals (n = 7 m...
Cell death was not observed in the corpus callosum three days after the stimulation at 300 Hz, and also not in sham-treated animals.
(A-C) Sham-treated animal: Coronal section of corpus callosum showing double channel immunofluorescent labelling with DAPI (A, blue), Caspase-3 (B, red), and the overlay of two channels (C). Left column: Overview imag...
Details on statistical analysis relevant to Fig 3L–3O.
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Details on statistical analysis relevant to Fig 1.
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Excel spreadsheets containing numerical data relevant to Fig 1.
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Details on statistical analysis relevant to Fig 3.
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Details on statistical analysis relevant to Fig 6.
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Details on statistical analysis relevant to Fig 8.
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Simultaneous application of ω-Conotoxin-GVIA and ω-Agatoxin-IVA reduces synaptic transmission but does not abolish it completely.
(A-C) Average current amplitude including failures, response probability, and response potency upon each stimulus of the train during control conditions and after perfusion of ω-Conotoxin-GVIA (Ctx) and ω-Agatoxin-IVA (A...
Excel spreadsheets containing numerical data relevant to Fig 3.
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Details on statistical analysis relevant to S1 Fig.
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Details on statistical analysis relevant to Fig 1.
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Details on statistical analysis relevant to Fig 2E and 2F.
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Details on statistical analysis relevant to Fig 3I–3J.
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Details on statistical analysis relevant to Fig 7.
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Details on statistical analysis relevant to S2 Fig.
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Microglia activation was not observed in the corpus callosum three days after the stimulation at 300 Hz, and also not in sham-treated animals.
(A-C) Sham-treated animal: Coronal section of corpus callosum from a showing double channel immunofluorescent labelling with DAPI (A, blue), CD68 (B, red), and the overlay of two channels (C). Left column: O...
Details on statistical analysis relevant to Fig 2G–2I.
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Details on statistical analysis relevant to Fig 2J–2L.
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Details on statistical analysis relevant to Fig 3F–3H.
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Details on statistical analysis relevant to Fig 2.
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Excel spreadsheets containing numerical data relevant to Fig 2.
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Details on statistical analysis relevant to Fig 4.
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Excel spreadsheets containing numerical data relevant to Fig 5.
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Excel spreadsheets containing numerical data relevant to Fig 7 and Fig 8.
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Excel spreadsheets containing numerical data relevant to S2 Fig.
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In the peripheral nervous system a vast number of axons are accommodated within fiber bundles that constitute peripheral nerves. A major function of peripheral axons is to propagate action potentials along their length, and hence they are equipped with Na+ and K+ channels, which ensure successful generation, conduction and termination of each actio...
The Jimpy mutant mouse has a point mutation in the proteolipid protein gene (plp1). The resulting misfolding of the protein leads to oligodendrocyte death, myelin destruction and failure to produce adequately myelinated axons in the central nervous system (CNS). It is not known how the absence of normal myelination during development influences neu...
Oligodendrocyte progenitor cells, OPCs, (also known as NG2-glia, polydendrocytes or synantocytes) are widespread in the grey and white matter areas of the central nervous system. In every region of the brain, OPCs are found as proliferative cells, and both in development and in the adult at least 50% of them are actively cycling. Signals responsibl...
The hyperpolarization-activated cation current I(h) is an important regulator of neuronal excitability and may contribute to the properties of the dentate gyrus granule (DGG) cells, which constitute the input site of the canonical hippocampal circuit. Here, we investigated changes in I(h) in DGG cells in human temporal lobe epilepsy (TLE) and the r...
The ubiquitous presynaptic metabotropic glutamate receptors (mGluRs) are generally believed to primarily inhibit synaptic transmission through blockade of Ca(2+) entry. Here, we analyzed how mGluR8 achieves a nearly complete inhibition of glutamate release at hippocampal synapses. Surprisingly, presynaptic Ca(2+) imaging and miniature excitatory po...
Progenitor cells expressing proteoglycan NG2 (also known as oligodendrocyte precursor cells or polydendrocytes) are widespread in the grey and white matter of the CNS; they comprise 8-9% of the total cell population in adult white matter, and 2-3% of total cells in adult grey matter. NG2 cells have a complex stellate morphology, with highly branche...
NG2-expressing oligodendrocyte precursor cells (OPCs) are ubiquitous and generate oligodendrocytes throughout the young and adult brain. Previous work has shown that virtually every NG2 cell receives synaptic input from many axons, but the meaning of this signaling is not understood. In particular, it is unclear whether neurons specifically synapse...
It is well established that NG2 cells throughout the young and adult brain consistently detect the release of single vesicles filled with glutamate from nearby axons. The released neurotransmitter glutamate electrically excites NG2 cells via non-NMDA (N-methyl-D-aspartic acid) glutamate receptors but the individual contribution of AMPA and kainate...
Progenitor cells expressing the proteoglycan NG2 represent approximately 5% of the total cells in the adult brain, and are found both in grey and white matter regions where they give rise to oligodendrocytes. The finding that these cells receive synaptic contacts from excitatory and inhibitory neurons has not only raised major interest in the possi...
In postnatal rodent brain, certain NG2-expressing oligodendroglial precursor cells (OPCs) are contacted by synaptic terminals from local neurons. However, it has remained elusive whether and when NG2(+) cells are integrated into neuronal circuits. Here we use patch-clamp recordings from mitotic cells in murine brain slices to show that, unlike any...
Removal of neurotransmitter from the extracellular space is crucial for normal functioning of the central nervous system. In this study, we have used high-affinity metabotropic glutamate receptors (mGluRs) expressed by hippocampal CA1 pyramidal cells to test how far bath-applied glutamate penetrates into slice tissue before being removed by uptake...
Vesicular release of neurotransmitter is the universal output signal of neurons in the brain. It is generally believed that fast transmitter release is restricted to nerve terminals that contact postsynaptic cells in the gray matter. Here we show in the rat brain that the neurotransmitter glutamate is also released at discrete sites along axons in...
The precise shape of action potentials in cortical neurons is a key determinant of action potential-dependent Ca2+ influx, as well as of neuronal signaling, on a millisecond scale. In cortical neurons, Ca2+-sensitive K+ channels, or BK channels (BKChs), are crucial for action potential termination, but the precise functional interplay between Ca2+...
In the hippocampus of chronic temporal lobe epilepsy, many abnormalities in structure and function have been described but their pathophysiological relevance often is poorly understood. In this study, we asked whether there may be a link between changes in the firing pattern and the loss of the calcium binding protein calbindin-D28k in epileptic hi...
Hippocampal mossy fiber synapses show unique molecular features and dynamic range of plasticity. A recent paper proposed that the defining features of mossy fiber synaptic plasticity are caused by a local buildup of extracellular adenosine (Moore et al., 2003). In this study, we reassessed the role of ambient adenosine in regulating mossy fiber syn...
Ca2+-binding proteins are ubiquitously expressed throughout the CNS and serve as valuable immunohistochemical markers for certain types of neurons. However, the functional role of most Ca2+-binding proteins has to date remained obscure because their concentration in central neurons is not known. In this study, we investigate the intracellular conce...
The ionotropic and cytolytic P2X7 receptor is typically found on immune cells, where it is involved in the release of cytokines. Recently, P2X7 receptors were reported to be localized to presynaptic nerve terminals and to modulate transmitter release. In the present study, we reassessed this unexpected role of P2X7 receptors at hippocampal mossy fi...
Ca2+ influx into presynaptic terminals via voltage-dependent Ca2+ channels triggers fast neurotransmitter release as well as different forms of synaptic plasticity. Using electrophysiological and genetic techniques we demonstrate that presynaptic Ca2+ entry through Cav2.3 subunits contributes to the induction of mossy fiber LTP and posttetanic pote...
Recent evidence suggested that ATP acting via ionotropic (P2X) and metabotropic (P2Y) purinergic receptors might be involved in signaling between glial cells and within glial-neuronal networks. In contrast to their neuronal counterpart, the identity of P2X receptors in CNS glial cells is largely unknown. In the present study, antibodies recognizing...
The proto-oncogene B-cell lymphoma protein 2 (BCL-2) and its homologues are important modulators of cellular survival after transient brain ischaemia. In the present study we used western blotting to elucidate if the stimulation of 5-hydroxytryptamine 1A type receptors with their agonist BAY X 3702 results in regulation of BCL-2 family proteins. Tr...
It has recently been shown that 5-HT(1A) receptor stimulation reduced the infarct volume after occlusion of the middle cerebral artery in rats. Since there is increasing evidence that apoptosis is involved in neurodegenerative diseases and stroke, we investigated whether the 5-HT(1A) agonist Bay x 3702 could protect neurons against apoptotic damage...
Rat brain subjected to 45-min global ischemia is characterized by decreased activity of K-p-nitrophenyl phosphatase and monoamine oxidase B and a disordering of the membrane bilayer by reactive oxygen species attack, the latter being monitored by the fluorescence of the membrane fluorescent probe, 1-anilino,8-naphtalene sulphonate (ANS). Ischemic i...
The effect of dietary carnosine on the behavioral and biochemical characteristics of rats under experimental ischemia was studied. Carnosine was shown to improve the animals orientation and learning in "Open Field" and "T-Maze" tests, and this effect was accompanied with an increase in glutamate binding to N-methyl-D-aspartate (NMDA) receptors in b...
Angiotensin-converting enzyme inhibitors have been demonstrated to protect spontaneously hypertensive rats from cerebral ischemia. The present study investigated the protective effect of enalapril and moexipril in models of permanent focal cerebral ischemia in normotensive mice and rats. To elucidate the mechanism of neuroprotection the influence o...
1. The biological effects of carnosine, a natural hydrophilic neuropeptide, on the reactive oxygen species (ROS) pathological generation are reviewed.
2. We describe direct antioxidant action observed in the in vitro experiments.
3. Carnosine was found to effect metabolism indirectly. These effects are reflected in ROS turnover regulation and lipid...
Flow structure and wall shear stress and the changes in these parameters induced by the administration of a drag-reducing polymer polyethylene oxide WSR-301 at a concentration of 10(-5) g/ml were studied in a glass tube with a T-junction by the laser Doppler anemometry technique. The pattern of wall shear stresses is in a good agreement with the da...
Flow structure and wall shear stress and the changes in these parameters induced by the administration of a drag-reducing polymer polyethylene oxide WSR-301 at a concentration of 10-5 g/ml were studied in a glass tube with a T-junction by the laser Doppler anemometry technique. The pattern of wall shear stresses is in a good agreement with the data...
The data about the role of blood flow in atherosclerosis development were examined. The aim of the study was determination of hydrodynamic blood resistance and Toms effect in patients with ischemic disorders of cerebral circulation in different periods of the disease. 45 patients with atherosclerotic damages of major arteries of head were observed....
It is found for each of the rat brain regions studied (cerebral cortex, subjacent white substance, and brainstem) that both
the initial levels of 2-thiobarbituric acid-reactive products and the rates of their increment are highest in rats resistant
to emotional stress and lowest in stress-prone rats, and that the rates at which lipid peroxidation p...
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