The pathological potential of glial cells was recognized already by Rudolf Virchow, Santiago Ramon y Cajal and Pio Del Rio-Ortega. Many functions and roles performed by astroglia in the healthy brain determine their involvement in brain diseases; as indeed any kind of brain insult does affect astrocytes, and their performance in pathological conditions, to a very large extent, determines the survival of the brain parenchyma, the degree of damage and neurological defect. Astrocytes being in general responsible for overall brain homeostasis are involved in virtually every form of brain pathology. Here we provide an overview of recent developments in identifying the role and mechanisms of the pathological potential of astroglia.
- MeSH
- astrocyty fyziologie ultrastruktura MeSH
- draslík analýza metabolismus MeSH
- extracelulární prostor chemie MeSH
- glióza patofyziologie MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mezerový spoj fyziologie MeSH
- mozek patologie fyziologie patofyziologie MeSH
- nemoci mozku patologie patofyziologie MeSH
- neurony fyziologie MeSH
- neurotransmiterové látky metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- synapse fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
Neuronal activity and many pathological states in the CNS are accompanied by transient astrocytic swelling, which affects excitability, extrasynaptic transmission, and neuron-glia interactions. By using three-dimensional confocal morphometry (3DCM), we quantified the morphometric parameters of astrocytes in intact tissue. In experiments performed in brain cortex slices from transgenic GFAP/EGFP mice, we applied 3DCM to study the dynamic changes in astrocyte morphology during hypotonic stress. Our morphometric analysis showed that the effect of a 10-min application of hypotonic solution (200 mmol/kg) on the swelling of different cell compartments was dependent on the extent of the swelling of the total astrocyte volume. If the swelling of the whole cell, i.e., soma and processes, was less than approximately 10%, there were no differences between the swelling of the soma and the processes. However, if the swelling of the total cell volume was greater than 10%, the swelling of the processes was greater than the swelling of the soma. Analyzing the effect of hypotonic solution on the morphology of these astrocytes revealed that the total cell volume increased; however, certain cell compartments were distinguished in which the volume increased, whereas in other compartments cell volume decreased or apparently did not change, and the structure of some compartments was altered. Our data show that astrocytes in brain slices undergoing hypotonic stress display cell volume regulation as well as transient changes in morphology.
- MeSH
- astrocyty ultrastruktura MeSH
- financování organizované MeSH
- gliový fibrilární kyselý protein genetika MeSH
- hypotonické roztoky MeSH
- konfokální mikroskopie MeSH
- mozek ultrastruktura MeSH
- myši transgenní MeSH
- myši MeSH
- orgánové kultury - kultivační techniky MeSH
- počítačové zpracování obrazu MeSH
- promotorové oblasti (genetika) MeSH
- zelené fluorescenční proteiny genetika MeSH
- zobrazování trojrozměrné MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- MeSH
- finanční podpora výzkumu jako téma MeSH
- Publikační typ
- abstrakty MeSH
[K(+)](e) increase accompanies many pathological states in the CNS and evokes changes in astrocyte morphology and glial fibrillary acidic protein expression, leading to astrogliosis. Changes in the electrophysiological properties and volume regulation of astrocytes during the early stages of astrocytic activation were studied using the patch-clamp technique in spinal cords from 10-day-old rats after incubation in 50 mM K(+). In complex astrocytes, incubation in high K(+) caused depolarization, an input resistance increase, a decrease in membrane capacitance, and an increase in the current densities (CDs) of voltage-dependent K(+) and Na(+) currents. In passive astrocytes, the reversal potential shifted to more positive values and CDs decreased. No changes were observed in astrocyte precursors. Under hypotonic stress, astrocytes in spinal cords pre-exposed to high K(+) revealed a decreased K(+) accumulation around the cell membrane after a depolarizing prepulse, suggesting altered volume regulation. 3D confocal morphometry and the direct visualization of astrocytes in enhanced green fluorescent protein/glial fibrillary acidic protein mice showed a smaller degree of cell swelling in spinal cords pre-exposed to high K(+) compared to controls. We conclude that exposure to high K(+), an early event leading to astrogliosis, caused not only morphological changes in astrocytes but also changes in their membrane properties and cell volume regulation.
- MeSH
- astrocyty fyziologie MeSH
- draslík farmakokinetika MeSH
- draslíkové kanály řízené napětím fyziologie MeSH
- financování organizované MeSH
- gliový fibrilární kyselý protein metabolismus MeSH
- glióza patofyziologie MeSH
- hypotonické roztoky farmakologie MeSH
- imunohistochemie MeSH
- koncentrace vodíkových iontů MeSH
- krysa rodu rattus MeSH
- membránové potenciály fyziologie účinky léků MeSH
- metoda terčíkového zámku MeSH
- mícha cytologie MeSH
- osmotický tlak MeSH
- potkani Wistar MeSH
- sodík metabolismus MeSH
- sodíkové kanály fyziologie MeSH
- velikost buňky MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
GFP labeled/NE-4C neural progenitor cells cloned from primary neuroectodermal cultures of p53- mouse embryos give rise to neurons when exposed to retinoic acid in vitro. To study their survival and differentiation in vivo, cells were transplanted into the cortex of 6-week-old rats, 1 week after the induction of a photochemical lesion or into noninjured cortex. The electrophysiological properties of GFP/NE-4C cells were studied in vitro (8-10 days after differentiation induction) and 4 weeks after transplantation using the whole-cell patch-clamp technique, and immunohistochemical analyses were carried out. After transplantation into a photochemical lesion, a large number of cells survived, some of which expressed the astrocytic marker GFAP. GFP/GFAP-positive cells, with an average resting membrane potential (Vrest) of -71.9 mV, displayed passive time- and voltage-independent K+ currents and, additionally, voltage-dependent A-type K+ currents (KA) and/or delayed outwardly rectifying K+ currents (KDR). Numerous GFP-positive cells expressed NeuN, betaIII-tubulin, or 68 kD neurofilaments. GFP/betaIII-tubulin-positive cells, with an average Vrest of -61.6 mV, were characterized by the expression of KA and KDR currents and tetrodotoxin-sensitive Na+ currents. GFP/NE-4C cells also gave rise to oligodendrocytes, based on the detection of oligodendrocyte-specific markers. Our results indicate that GFP/NE-4C neural progenitors transplanted into the site of a photochemical lesion give rise to neurons and astrocytes with membrane properties comparable to those transplanted into noninjured cortex. Therefore, GFP/NE-4C cells provide a suitable model for studying neuro- and gliogenesis in vivo. Further, our results suggest that embryonic neuroectodermal progenitor cells may hold considerable promise for the repair of ischemic brain lesions.
- MeSH
- antitumorózní látky farmakologie MeSH
- astrocyty fyziologie MeSH
- buněčná diferenciace účinky léků MeSH
- buněčné linie MeSH
- denervace metody MeSH
- ektoderm cytologie MeSH
- financování organizované MeSH
- fotosenzibilizující látky MeSH
- imunohistochemie MeSH
- ischemie mozku patologie terapie MeSH
- kmenové buňky cytologie fyziologie MeSH
- membránové potenciály MeSH
- metoda terčíkového zámku MeSH
- modely nemocí na zvířatech MeSH
- mozková kůra fyziologie chirurgie patologie MeSH
- myši MeSH
- neurony cytologie fyziologie MeSH
- oligodendroglie fyziologie MeSH
- přežívání štěpu MeSH
- transplantace kmenových buněk MeSH
- tretinoin farmakologie MeSH
- zelené fluorescenční proteiny genetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- MeSH
- psychoterapie MeSH
- vztahy mezi lékařem a pacientem MeSH
- Publikační typ
- recenze MeSH