Human cellular models of neurodegeneration require reproducibility and longevity, which is necessary for simulating age-dependent diseases. Such systems are particularly needed for TDP-43 proteinopathies1, which involve human-specific mechanisms2-5 that cannot be directly studied in animal models. Here, to explore the emergence and consequences of TDP-43 pathologies, we generated induced pluripotent stem cell-derived, colony morphology neural stem cells (iCoMoNSCs) via manual selection of neural precursors6. Single-cell transcriptomics and comparison to independent neural stem cells7 showed that iCoMoNSCs are uniquely homogenous and self-renewing. Differentiated iCoMoNSCs formed a self-organized multicellular system consisting of synaptically connected and electrophysiologically active neurons, which matured into long-lived functional networks (which we designate iNets). Neuronal and glial maturation in iNets was similar to that of cortical organoids8. Overexpression of wild-type TDP-43 in a minority of neurons within iNets led to progressive fragmentation and aggregation of the protein, resulting in a partial loss of function and neurotoxicity. Single-cell transcriptomics revealed a novel set of misregulated RNA targets in TDP-43-overexpressing neurons and in patients with TDP-43 proteinopathies exhibiting a loss of nuclear TDP-43. The strongest misregulated target encoded the synaptic protein NPTX2, the levels of which are controlled by TDP-43 binding on its 3' untranslated region. When NPTX2 was overexpressed in iNets, it exhibited neurotoxicity, whereas correcting NPTX2 misregulation partially rescued neurons from TDP-43-induced neurodegeneration. Notably, NPTX2 was consistently misaccumulated in neurons from patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration with TDP-43 pathology. Our work directly links TDP-43 misregulation and NPTX2 accumulation, thereby revealing a TDP-43-dependent pathway of neurotoxicity.

• MeSH
• amyotrofická laterální skleróza * metabolismus   patologie   MeSH
• C-reaktivní protein * metabolismus   MeSH
• DNA vazebné proteiny * nedostatek   metabolismus   MeSH
• frontotemporální lobární degenerace * metabolismus   patologie   MeSH
• lidé MeSH
• nervová síť * metabolismus   patologie   MeSH
• nervové kmenové buňky cytologie   MeSH
• neuroglie cytologie   MeSH
• neurony * cytologie   metabolismus   MeSH
• proteiny nervové tkáně * metabolismus   MeSH
• reprodukovatelnost výsledků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• C-reaktivní protein * MeSH
• DNA vazebné proteiny * MeSH
• neuronal pentraxin MeSH Prohlížeč
• proteiny nervové tkáně * MeSH
• TARDBP protein, human MeSH Prohlížeč

Neuropeptides including oxytocin belong to the group of factors that may play a role in the control of neuronal cell survival, proliferation and differentiation. The aim of the present study was to investigate potential contribution of oxytocin to neuronal differentiation by measuring gene and protein expression of specific neuron and glial markers in the brain. Neonatal and adult oxytocin administration was used to reveal developmental and/or acute effects of oxytocin in Wistar rats. Gene and protein expression of neuron-specific enolase (NSE) in the hippocampus was increased in 21-day and 2-month old rats in response to neonatal oxytocin administration. Neonatal oxytocin treatment induced a significant increase of gene and protein expression of the marker of astrocytes - glial fibrillary acid protein (GFAP). Oxytocin treatment resulted in a decrease of oligodendrocyte marker mRNA - 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) - in 21-day and 2-month old rats, while no change of CD68 mRNA, marker of microglia, was observed. Central oxytocin administration in adult rats induced a significant increase of gene expression of NSE and CNPase. The present study provides the first data revealing the effect of oxytocin on the expression of neuron and glial markers in the brain. It may be suggested that the oxytocin system is involved in the regulation of development of neuronal precursor cells in the brain.

• MeSH
• 2',3'-cyklické nukleotidfosfodiesterasy genetika   MeSH
• antigeny diferenciační myelomonocytární genetika   MeSH
• CD antigeny genetika   MeSH
• hipokampus cytologie   účinky léků   metabolismus   MeSH
• krysa rodu Rattus MeSH
• neuroglie cytologie   účinky léků   metabolismus   MeSH
• neurony cytologie   účinky léků   metabolismus   MeSH
• oxytocin farmakologie   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 2',3'-cyklické nukleotidfosfodiesterasy MeSH
• antigeny diferenciační myelomonocytární MeSH
• CD antigeny MeSH
• CD68 antigen, human MeSH Prohlížeč
• oxytocin MeSH

The previous works of Purkyně, Valentin, and Remak showed that the central and peripheral nervous systems contained not only nerve fibers but also cellular elements. The use of microscopes and new fixation techniques enabled them to accurately obtain data on the structure of nerve tissue and consequently in many European universities microscopes started to become widely used in histological and morphological studies. The present review summarizes important discoveries concerning the structure of neural tissue, mostly from vertebrates, during the period from 1838 to 1865. This review describes the discoveries of famous as well as less well-known scholars of the time, who contributed significantly to current understandings about the structure of neural tissue. The period is characterized by the first descriptions of different types of nerve cells and the first attempts of a cytoarchitectonic description of the spinal cord and brain. During the same time, the concept of a neuroglial tissue was introduced, first as a tissue for "gluing" nerve fibers, cells, and blood capillaries into one unit, but later some glial cells were described for the first time. Questions arose as to whether or not cells in ganglia and the central nervous system had the same morphological and functional properties, and whether nerve fibers and cell bodies were interconnected. Microscopic techniques started to be used for the examination of physiological as well as pathological nerve tissues. The overall state of knowledge was just a step away from the emergence of the concept of neurons and glial cells.

• Klíčová slova
• Brain, fibers, ganglia, glia, history, nerves, nineteenth century, structure,
• MeSH
• centrální nervový systém anatomie a histologie   cytologie   MeSH
• dějiny 19. století MeSH
• dějiny 20. století MeSH
• ganglia anatomie a histologie   MeSH
• histologické techniky dějiny   metody   MeSH
• lékařské ilustrace dějiny   MeSH
• mikroskopie dějiny   MeSH
• mozek anatomie a histologie   MeSH
• nervová tkáň anatomie a histologie   cytologie   MeSH
• neuroanatomie dějiny   MeSH
• neuroglie cytologie   MeSH
• neurony cytologie   MeSH
• zvířata MeSH
• Check Tag
• dějiny 19. století MeSH
• dějiny 20. století MeSH
• zvířata MeSH
• Publikační typ
• biografie MeSH
• časopisecké články MeSH
• historické články MeSH
• přehledy MeSH

• O autorovi
• Purkyně, Jan
• Mauthner, Ludwig

The canonical Wnt signaling pathway plays an important role in embryogenesis, and the establishment of neurogenic niches. It is involved in proliferation and differentiation of neural progenitors, since elevated Wnt/β-catenin signaling promotes differentiation of neural stem/progenitor cells (NS/PCs1) towards neuroblasts. Nevertheless, it remains elusive how the differentiation program of neural progenitors is influenced by the Wnt signaling output. Using transgenic mouse models, we found that in vitro activation of Wnt signaling resulted in higher expression of β-catenin protein and Wnt/β-catenin target genes, while Wnt signaling inhibition resulted in the reverse effect. Within differentiated cells, we identified three electrophysiologically and immunocytochemically distinct cell types, whose incidence was markedly affected by the Wnt signaling output. Activation of the pathway suppressed gliogenesis, and promoted differentiation of NS/PCs towards a neuronal phenotype, while its inhibition led to suppressed neurogenesis and increased counts of cells of glial phenotype. Moreover, Wnt signaling hyperactivation resulted in an increased incidence of cells expressing outwardly rectifying K+ currents, together with inwardly rectifying Na+ currents, a typical current pattern of immature neurons, while blocking the pathway led to the opposite effect. Taken together, our data indicate that the Wnt signaling pathway orchestrates neonatal NS/PCs differentiation towards cells with neuronal characteristics, which might be important for nervous tissue regeneration during central nervous system disorders. Furthermore, the transgenic mouse strains used in this study may serve as a convenient tool to manipulate β-catenin-dependent signaling in neural progenitors in the neonatal brain.

• Klíčová slova
• Gliogenesis, Ion channel, Neonatal mouse, Neurogenesis, Patch-clamp technique, β-catenin signaling,
• MeSH
• beta-katenin genetika   metabolismus   MeSH
• imunohistochemie MeSH
• kultivované buňky MeSH
• membránové potenciály fyziologie   MeSH
• metoda terčíkového zámku MeSH
• mezibuněčné signální peptidy a proteiny genetika   metabolismus   MeSH
• mozek cytologie   metabolismus   MeSH
• myši transgenní MeSH
• nervové kmenové buňky cytologie   metabolismus   MeSH
• neurogeneze fyziologie   MeSH
• neuroglie cytologie   metabolismus   MeSH
• neurony cytologie   metabolismus   MeSH
• signální dráha Wnt fyziologie   MeSH
• transkripční faktor 4 MeSH
• transkripční faktory BHLH-Zip genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• beta-katenin MeSH
• CTNNB1 protein, mouse MeSH Prohlížeč
• Dkk1 protein, mouse MeSH Prohlížeč
• mezibuněčné signální peptidy a proteiny MeSH
• Tcf4 protein, mouse MeSH Prohlížeč
• transkripční faktor 4 MeSH
• transkripční faktory BHLH-Zip MeSH

Non-thermal plasma has been recognized as a promising tool across a vast variety of biomedical applications, with the potential to create novel therapeutic methods. However, the understanding of the molecular mechanisms behind non-thermal plasma cellular effects remains a significant challenge. In this study, we show how two types of different non-thermal plasmas induce cell death in mammalian cell cultures via the formation of multiple intracellular reactive oxygen/nitrogen species. Our results showed a discrepancy in the superoxide accumulation and lysosomal activity in response to air and helium plasma, suggesting that triggered signalling cascades might be grossly different between different plasmas. In addition, the effects of ozone, a considerable component of non-thermal plasma, have been simultaneously evaluated and have revealed much faster and higher cytotoxic effects. Our findings offer novel insight into plasma-induced cellular responses, and provide a basis for better controlled biomedical applications.

• MeSH
• acetylcystein farmakologie   MeSH
• annexin A5 MeSH
• antioxidancia farmakologie   MeSH
• buněčná smrt účinky léků   MeSH
• buňky 3T3 MeSH
• helium chemie   MeSH
• krysa rodu Rattus MeSH
• lyzozomy účinky léků   MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• neuroglie cytologie   účinky léků   metabolismus   MeSH
• ozon chemie   MeSH
• plazmové plyny farmakologie   MeSH
• reaktivní formy dusíku agonisté   antagonisté a inhibitory   metabolismus   MeSH
• reaktivní formy kyslíku agonisté   antagonisté a inhibitory   metabolismus   MeSH
• signální transdukce MeSH
• viabilita buněk účinky léků   MeSH
• vzduch MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylcystein MeSH
• annexin A5 MeSH
• antioxidancia MeSH
• helium MeSH
• ozon MeSH
• plazmové plyny MeSH
• reaktivní formy dusíku MeSH
• reaktivní formy kyslíku MeSH

Astrocytes perform control and regulatory functions in the central nervous system; heterogeneity among them is still a matter of debate due to limited knowledge of their gene expression profiles and functional diversity. To unravel astrocyte heterogeneity during postnatal development and after focal cerebral ischemia, we employed single-cell gene expression profiling in acutely isolated cortical GFAP/EGFP-positive cells. Using a microfluidic qPCR platform, we profiled 47 genes encoding glial markers and ion channels/transporters/receptors participating in maintaining K(+) and glutamate homeostasis per cell. Self-organizing maps and principal component analyses revealed three subpopulations within 10-50 days of postnatal development (P10-P50). The first subpopulation, mainly immature glia from P10, was characterized by high transcriptional activity of all studied genes, including polydendrocytic markers. The second subpopulation (mostly from P20) was characterized by low gene transcript levels, while the third subpopulation encompassed mature astrocytes (mainly from P30, P50). Within 14 days after ischemia (D3, D7, D14), additional astrocytic subpopulations were identified: resting glia (mostly from P50 and D3), transcriptionally active early reactive glia (mainly from D7) and permanent reactive glia (solely from D14). Following focal cerebral ischemia, reactive astrocytes underwent pronounced changes in the expression of aquaporins, nonspecific cationic and potassium channels, glutamate receptors and reactive astrocyte markers.

• MeSH
• antigeny genetika   metabolismus   MeSH
• astrocyty metabolismus   MeSH
• gliový fibrilární kyselý protein genetika   metabolismus   MeSH
• imunohistochemie MeSH
• mozková kůra cytologie   metabolismus   MeSH
• myši transgenní MeSH
• myši MeSH
• neuroglie cytologie   metabolismus   MeSH
• polymerázová řetězová reakce MeSH
• proteoglykany genetika   metabolismus   MeSH
• průtoková cytometrie MeSH
• S-100 kalcium vázající protein G, podjednotka beta genetika   metabolismus   MeSH
• zelené fluorescenční proteiny genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny MeSH
• chondroitin sulfate proteoglycan 4 MeSH Prohlížeč
• enhanced green fluorescent protein MeSH Prohlížeč
• gliový fibrilární kyselý protein MeSH
• proteoglykany MeSH
• S-100 kalcium vázající protein G, podjednotka beta MeSH
• zelené fluorescenční proteiny MeSH

BACKGROUND AIMS: Olfactory ensheathing glia (OEG) and mesenchymal stromal cells (MSC) are suitable candidates for transplantation therapy of spinal cord injury (SCI). Both facilitate functional improvement after SCI by producing trophic factors and cytokines. In this study, the co-transplantation of both types of cells was studied to clarify their additive and/ or synergistic effects on SCI. METHODS: A balloon-induced compression lesion was used to produce SCI in rats. OEG, MSC or both OEG and MSC (3 x 10(5) cells of each cell type) were implanted by intraspinal injection 1 week after SCI. The effect of transplantation was assessed using behavioral, electrophysiologic and histologic methods. RESULTS: Hindlimb function was examined with Basso, Beattie and Bresnahan (BBB) and Plantar tests. Improvement was found in all three groups of transplanted rats with different time-courses, but there was no significant difference among the groups at the end of the experiment. Motor-evoked potentials after SCI decreased in amplitude from 7 mV to 10 microV. Linear regression analysis showed a modest recovery in amplitude following transplantation, but no change in the control rats. Histologic findings showed that the white and gray matter were significantly spared by transplantation after SCI. CONCLUSIONS: Functional improvement was achieved with transplantation of OEG and/or MSC, but the co-transplantation of OEG and MSC did not show synergistic effects. The poor migration of OEG and MSC might prevent their concerted action. Pre-treatment with a Rho antagonist and a combination of intraspinal and intravenous injection of the cells might be beneficial for SCI therapy.

• MeSH
• bulbus olfactorius cytologie   MeSH
• buňky stromatu cytologie   transplantace   MeSH
• krysa rodu Rattus MeSH
• mezenchymální kmenové buňky cytologie   MeSH
• motorické evokované potenciály fyziologie   MeSH
• neuroglie cytologie   transplantace   MeSH
• obnova funkce fyziologie   MeSH
• pohybová aktivita fyziologie   MeSH
• poranění míchy patologie   patofyziologie   terapie   MeSH
• potkani Sprague-Dawley MeSH
• potkani Wistar MeSH
• transplantace mezenchymálních kmenových buněk * MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Neural progenitors of the mouse forebrain can be propagated in vitro as neurospheres in the presence of bFGF and EGF. However, less is understood whether regional characteristics or developmental stage properties of these cells are maintained in neurosphere cultures. Here we show that the original cell fate is lost in neurosphere cultures. We isolated neural progenitors from the dorsal telencephalon of D6-GFP mice and cultured them in vitro. The expression profile was specifically changed in cultured cells in just three passages. Markers of the dorsal forebrain were downregulated and several ventrally-expressed genes were induced. The altered gene expression led to a profound phenotypic change of cultured cells. D6-GFP positive cortical progenitors produce excitatory neurons in the cortex and few astrocytes in vivo but after culture in vitro, these cells differentiate into many astrocytes and also oligodendrocytes and inhibitory neurons. Wnt signaling in cultured neurospheres was downregulated in the same manner as other dorsal markers but dominant active Wnt signaling slowed down the loss of the dorsal identity in neurospheres.

• MeSH
• astrocyty cytologie   metabolismus   MeSH
• buněčná diferenciace fyziologie   MeSH
• buněčné sféroidy cytologie   MeSH
• buněčný rodokmen fyziologie   MeSH
• genetické markery genetika   MeSH
• interneurony cytologie   metabolismus   MeSH
• kmenové buňky cytologie   metabolismus   MeSH
• mozková kůra cytologie   embryologie   metabolismus   MeSH
• myši transgenní MeSH
• myši MeSH
• neuroglie cytologie   metabolismus   MeSH
• neurony cytologie   metabolismus   MeSH
• oligodendroglie cytologie   metabolismus   MeSH
• promotorové oblasti (genetika) genetika   MeSH
• rekombinantní fúzní proteiny genetika   MeSH
• telencefalon cytologie   embryologie   metabolismus   MeSH
• vývojová regulace genové exprese genetika   MeSH
• zelené fluorescenční proteiny genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• genetické markery MeSH
• rekombinantní fúzní proteiny MeSH
• zelené fluorescenční proteiny MeSH

PURPOSE: To examine the morphologic alterations in the cerebral cortex and hippocampus of immature rats 6 days after the generalized clonic-tonic seizures induced by homocysteic acid (HCA). METHODS: Seizures were induced by bilateral intracerebroventricular infusion of HCA (600 nmol per each side) in 12-day-old rats. After 6 days, rat pups were transcardially perfused under deep ether anesthesia with heparinized normal saline and subsequently with the fixation solution (4% paraformaldehyde in phosphate buffer, pH 7.4, for light microscopy) or with Karnovsky's solution (4% paraformaldehyde and 2% glutaraldehyde in phosphate buffer, pH 7.4, for electron microscopic analysis). Nissl stain and the DNA-specific dye bis-benzimide (Hoechst 33342) were used. RESULTS: No pathologic changes were found in the cerebral cortex, whereas serious alterations occurred in the hippocampus. A total loss of CA3 pyramidal cells was observed, with marked changes in the CA1 region and dentate gyrus. A prominent glial reaction was seen in many regions of the hippocampal formation. A slight dilatation of the cerebral ventricles was noticed in some experimental as well as control animals. In the granule cell layer of the dentate gyrus, neurons with segmented or fragmented nuclei in various stages of degeneration were detected, displaying the features of apoptotic death. CONCLUSIONS: These findings demonstrate the vulnerability of the immature rat brain, which most likely reflects both the direct neurotoxic effect of HCA and prolonged seizure activity. The relative contribution of these two factors still remains to be assessed.

• MeSH
• apoptóza * fyziologie   MeSH
• buněčné jádro patologie   MeSH
• degenerace nervu patologie   MeSH
• gyrus dentatus cytologie   účinky léků   patologie   MeSH
• hipokampus cytologie   účinky léků   patologie   MeSH
• homocystein * analogy a deriváty   farmakologie   MeSH
• krysa rodu Rattus MeSH
• mozková kůra cytologie   účinky léků   patologie   MeSH
• neuroglie cytologie   patologie   MeSH
• neurony cytologie   účinky léků   patologie   MeSH
• novorozená zvířata MeSH
• počet buněk MeSH
• potkani Wistar MeSH
• pyramidové buňky cytologie   patologie   MeSH
• záchvaty chemicky indukované   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• homocysteic acid MeSH Prohlížeč
• homocystein * MeSH

In rat brain and spinal cord slices, the local extracellular accumulation of K(+), as indicated by K(+) tail currents (I(tail)) after a depolarization step, is greater in the vicinity of oligodendrocytes than that of astrocytes. It has been suggested that this may reflect a smaller extracellular space (ECS) around oligodendrocytes compared to astrocytes [Chvátal et al. [1997] J. Neurosci. Res. 49:98-106; [1999] J. Neurosci. Res. 56:493-505). We therefore compared the effect of osmotic stress in spinal cord slices from 5-11-day-old rats on the changes in reversal potentials (V(rev)) of I(tail) measured by the whole-cell patch-clamp technique and the changes in ECS volume measured by the real-time iontophoretic method. Cell swelling induced by a 20 min perfusion of hypoosmotic solution (200 mmol/kg) decreased the ECS volume fraction from 0.21 +/- 0.01 to 0.15 +/- 0.02, i.e., by 29%. As calculated from V(rev) of I(tail) using the Nernst equation, a depolarizing prepulse increased [K(+)](e) around astrocytes from 11.0 to 44.7 mM, i.e., by 306%, and around oligodendrocytes from 26.1 to 54.9 mM, i.e., by 110%. The ECS volume fraction decrease had the same time course as the changes in V(rev) of I(tail). Cell shrinkage in hyperosmotic solution (400 mmol/kg) increased ECS volume fraction from 0.24 +/- 0.02 to 0.32 +/- 0.02, i.e., by 33%. It had no effect on [K(+)](e) evoked by a depolarizing prepulse in astrocytes, whereas in oligodendrocytes [K(+)](e) rapidly decreased from 52 to 26 mM, i.e., by 50%. The increase in ECS volume was slower than the changes in [K(+)](e). These data demonstrate that hypoosmotic solution has a larger effect on the ECS volume around astrocytes than around oligodendrocytes and that hyperosmotic solution affects the ECS volume around oligodendrocytes only. This indicates that increased K(+) accumulation in the vicinity of oligodendrocytes could be due to a restricted ECS. Oligodendrocytes in the CNS are therefore most likely surrounded by clusters of "compacted" ECS, which may selectively affect the diffusion of neuroactive substances in specific areas and directions and facilitate spatial K(+) buffering.

• MeSH
• astrocyty cytologie   metabolismus   MeSH
• buněčná membrána metabolismus   ultrastruktura   MeSH
• draslík metabolismus   MeSH
• draslíkové kanály metabolismus   MeSH
• elektrická stimulace MeSH
• extracelulární prostor metabolismus   MeSH
• fyziologický stres metabolismus   patofyziologie   MeSH
• krysa rodu Rattus MeSH
• membránové potenciály fyziologie   MeSH
• mícha cytologie   metabolismus   MeSH
• neuroglie cytologie   metabolismus   MeSH
• oligodendroglie cytologie   metabolismus   MeSH
• orgánové kultury - kultivační techniky MeSH
• osmolární koncentrace MeSH
• osmotický tlak MeSH
• permeabilita buněčné membrány fyziologie   MeSH
• velikost buňky fyziologie   MeSH
• vodní a elektrolytová rovnováha fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• draslík MeSH
• draslíkové kanály MeSH