1,721,047 research outputs found
Ultrastructural localization of NGF receptors in satellite cells of the rat spinal ganglia
No full textData on the presence of NGF receptors in the satellite cells of spinal ganglia are scanty and contradictory. In the present study we used immunocytochemistry to examine the distribution of these receptors in spinal ganglia of the adult rat by light and electron microscopy. We found that (1) all satellite cells were immmunoreactive to p75 and the mean density of gold particles (mean number per microm2) was significantly greater in the satellite cell sheath than in the nerve cell body; (2) numerous satellite cells were immunoreactive for trkA with a mean density of gold particles slightly greater in the satellite cell sheath than in the nerve cell body, although the difference was not statistically significant; (3) both p75 and trkA immunoreactivity were confined to the cytoplasm. We suggest that the p75 receptor may be involved in the NGF-induced outgrowth of slender projections from the nerve cell body surface. With regard to the trkA receptor, satellite cells might be supported trophically by NGF released from the neuron with which they are associated; alternatively, satellite cells might internalize NGF to constitute a reservoir for later release to the neuron
Computational Characterization of tartrate-based TACE inhibitors
No full textSmall-molecule inhibitors of Tumor Necrosis factor alpha Converting Enzyme (TACE) are a
promising therapeutic tool for Rheumatoid Arthritis, Multiple Sclerosis and other autoimmune
diseases. Here we report on Hamiltonian Replica Exchange Molecular dynamics simulations of
three tartrate-based TACE inhibitors. The simulations show that irrespective of the inhibition
constant, the three drugs in bulk solvent adopt a common compact conformation whereby the
hydrophobic right-hand side and left-hand side substituents are packed against each other and the
hydroxyls necessary for Zinc chelation in the TACE active site are exposed toward the solvent.
Since the drugs in complex with TACE are expected to be in the extended conformation, our results
support the hypothesis of a structural rearrangement upon ligand binding. The proposed mechanism
may have important implications for the rational drug design
An ab initio force field for teh cofactors of bacterial photosynthesis
No full textThis article presents a new ab initio force field for the cofactors of bacterial photosynthesis, namely quinones and bacteriochlorophylls. The parameters has been designed to be suitable for molecular dynamics simulations of photosynthetic proteins by being compatible with the AMBER force field. To our knowledge, this is the first force field for photosynthetic cofactors based on a reliable set of ab initio density functional reference data for methyl bacteriochlorophyll a, methyl bacteriopheophytin a, and of a derivative of ubiquinone. Indeed, the new molecular mechanics force field is able to reproduce very well not only the experimental and ab initio structural properties and the vibrational spectra of the molecules, but also the eigenvectors of the molecular normal modes. For this reason it might also be helpful to understand vibrational spectroscopy results obtained on reaction center proteins
Perineuronal satellite cells in mouse spinal ganglia express the gap junction protein connexin43 throughout life with decline in old age
No full textSatellite glial cells that envelope the bodies of sensory neurons in spinal ganglia are connected to each other by gap junctions and exhibit dye coupling. These junctions may endow perineuronal satellite cells with the coordination necessary for the efficient performance of functions such as buffering of K(+) in the perineuronal microenvironment, provision of metabolic support to ganglionic neurons, and neuroprotection. Our knowledge of gap junctions has increased considerably in recent years, but little information is available on the connexins that form these junctions in spinal ganglia. In the present study we set out to determine whether the perineuronal satellite cells of mouse spinal ganglia express the connexins that are mainly present in neuroglial cells (Cx32 and Cx43). In young (3 months) mice, PCR showed the presence of both Cx32 and Cx43 transcripts. By immunocytochemistry, we localized Cx32 to axon-ensheathing Schwann cells, but not to other parts of the ganglion. We found Cx43 positivity in the perineuronal satellite cells, which were identified by their immunoreactivity to S100 protein and to glutamine synthetase. PCR showed Cx43 transcripts also in the spinal ganglia of adult (8 months) and old (24 months) animals. Cx43 immunostaining was present in satellite cells surrounding all nerve cell bodies, irrespective of size. The mean number of Cx43-immunoreactive puncta was significantly lower in the perineuronal satellite cells of aged mice compared to young and adult animals. This latter finding is consistent with observations in non-nervous tissues, and the hypothesis that a prominent decrease in Cx43 is a marker of senescence
Le cellule satelliti dei gangli spinali del ratto esprimono i recettori per il Nerve Growth Factor (NGF)
No full textABSTRACT. -Satellite cells from spinal ganglia of the adult rat express NGF receptors. Data on the presence of NGF receptors in the satellite cells of spinal ganglia are scanty and contradictory. In the present study we used immunocytochestry to examine the distribution of these receptors in spinal ganglia of the adult rat by light and electron microscopy. We found that (1) all satellite cells were immunoreactive to p75 and the mean density of gold particles (mean number per μm2) was significantly greater in the satellite cell sheath than in the nerve cell body; (2) numerous satellite cells were immunoreactive for trkA with a mean density of gold particles slightly greater in the satellite cell sheath than in the nerve cell body, although the difference was not statistically significant; (3) both p75 and trkA immunoreactivity were confined to the cytoplasm. We suggest that the p75 receptor may be involved in the NGF-induced outgrowth of slender projections from the nerve cell body surface. With regard to the trkA receptor, satellite cells might be supported trophically by NGF released from the neuron with which they are associated; alternatively, satellite cells might internalize NGF to constitute a reservoir for later release to the neuron
Empirical force field for the simulation of a class of chromophores in a photosynthetic center
No full textDecrease in the volume ratio between satellite cell sheaths and nerve cell bodies in the rabbit spinal ganglia with advancing age
No full textGABA-A and GABA-B mediated effects in the peripheral nervous system : a cross-interaction with neuroactive steroids
No full textSatellite glial cells in mouse spinal ganglia express connexin 43 throughout life
No full textIn spinal ganglia satellite cells that envelope each nerve cell body are connected to each other by gap junctions. These junctions form transmembrane channels that are implicated in intercellular communications and control the ions and small molecules passage. They may endow perineuronal satellite cells with the coordination necessary for the efficient performance of functions such as buffering of K+ in the perineuronal microenvironment, and neuroprotection. Our knowledge of gap junctions has increased considerably in recent years, in particular, studies on the central and the peripheral nervous systems have concurred to identify different types of connexin in the glial cells, such as astrocytes, oligodendrocytes, and Schwann cells, but little information is available on the connexins that form these junctions in spinal ganglia. In the present study we set out to determine whether the perineuronal satellite cells of mouse spinal ganglia express the connexins that are mainly present in neuroglial cells (i. e. Cx32 and Cx43).
Using Reverse Transcriptase-PCR we demonstrated that in the spinal ganglia of young mice (3-months old) the Cx32 transcript is present at low levels, while the Cx43 transcript is present at high levels. By immunocytochemistry, we localized Cx32 to the Schwann cells of nerve fibers, but not to other parts of the ganglion. Double-immunofluorescence labeling showed Cx43 positivity in the perineuronal satellite cells, which were identified by their immunoreactivity to S100 protein and to glutamine synthetase. Cx43 immunostaining was present in satellite cells sur¬rounding all nerve cell bodies, irrespective of size.
We also determined whether expression of Cx43 undergoes changes with age. To this aim digital confocal images from 3 age groups (3-months old, 8-months old, and 24-months old mice) were post-processed using ImageJ 1.36b image analysis software. Quantification of punctate signals of Cx43 associated with perineuronal satellite cells (as revealed by the S100 and glutamine synthetase labeling) was performed. It was found that the mean number of Cx43-immunoreactive puncta (per 500 μm2) is significantly lower in the perineuronal satellite cells of aged mice (1.18 ± 0.1) compared to young (2.88 ± 0.2) and adult (2.97 ± 0.18) animals. This latter finding is consistent with observations in non nervous tissues, and the hypothesis that a prominent decrease in Cx43 is a marker of senescence
Systemic inflammation alters satellite glial cell function and structure : a possible contribution to pain
No full textLocal peripheral injury activates satellite glial cells (SGCs) in sensory ganglia, which may contribute to chronic pain. We hypothesized that systemic inflammation affects sensory ganglia like local injury. We induced systemic inflammation in mice by injecting lipopolysaccharide (LPS) intraperitoneally, and characterized SGCs and neurons in dorsal root ganglia (DRG), using dye injection, calcium imaging, electron microscopy (EM), immunohistochemistry, and electrical recordings. Several days post-LPS, SGCs were activated, and dye coupling among SGCs increased 3-4.5-fold. EM showed abnormal growth of SGC processes and the formation of new gap junctions. Sensitivity of SGCs to ATP increased twofold, and neuronal excitability was augmented. Blocking gap junctions reduced pain behavior in LPS-treated mice. Thus, changes in DRG due to systemic inflammation are similar to those due to local injury, which may explain the pain in sickness behavior and in other systemic diseases
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