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- Adjan, V. V., et al.
(författare)
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Caspase-3 activity is reduced after spinal cord injury in mice lacking dynorphin : differential effects on glia and neurons
- 2007
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Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 148:3, s. 724-36
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Tidskriftsartikel (refereegranskat)abstract
- Dynorphins are endogenous opioid peptide products of the prodynorphin gene. An extensive literature suggests that dynorphins have deleterious effects on CNS injury outcome. We thus examined whether a deficiency of dynorphin would protect against tissue damage after spinal cord injury (SCI), and if individual cell types would be specifically affected. Wild-type and prodynorphin(-/-) mice received a moderate contusion injury at 10th thoracic vertebrae (T10). Caspase-3 activity at the injury site was significantly decreased in tissue homogenates from prodynorphin(-/-) mice after 4 h. We examined frozen sections at 4 h post-injury by immunostaining for active caspase-3. At 3-4 mm rostral or caudal to the injury, >90% of all neurons, astrocytes and oligodendrocytes expressed active caspase-3 in both wild-type and knockout mice. At 6-7 mm, there were fewer caspase-3(+) oligodendrocytes and astrocytes than at 3-4 mm. Importantly, caspase-3 activation was significantly lower in prodynorphin(-/-) oligodendrocytes and astrocytes, as compared with wild-type mice. In contrast, while caspase-3 expression in neurons also declined with further distance from the injury, there was no effect of genotype. Radioimmunoassay showed that dynorphin A(1-17) was regionally increased in wild-type injured versus sham-injured tissues, although levels of the prodynorphin processing product Arg(6)-Leu-enkephalin were unchanged. Our results indicate that dynorphin peptides affect the extent of post-injury caspase-3 activation, and that glia are especially sensitive to these effects. By promoting caspase-3 activation, dynorphin peptides likely increase the probability of glial apoptosis after SCI. While normally beneficial, our findings suggest that prodynorphin or its peptide products become maladaptive following SCI and contribute to secondary injury.
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| 2. |
- Ahuja, Poonam, et al.
(författare)
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Decreased glutathione transferase levels in rd1/rd1 mouse retina: Replenishment protects photoreceptors in retinal explants.
- 2005
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Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 131:4, s. 935-943
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Tidskriftsartikel (refereegranskat)abstract
- Currently much attention is focused on glutathione S transferase (GST)-induced suppression of apoptosis. The objective of our studies was therefore to see if GST isoenzymes rescue photoreceptors in retinal explants from rd1/rd1 mice, in which photoreceptors degenerate rapidly. Eyes from C3H rd1/rd1 and +/+ mice were collected at various time points between postnatal day (PN) 2 and PN28. Localization and content of alpha-GST and mu-GST was investigated by immunofluorescence and semi-quantitative Western blot analysis, respectively. In addition, PN2 and PN7 retinal explants were cultured till PN28, during which they were treated with 10 ng/ml alpha-GST or mu-GST. The spatiotemporal expression of both GST isoforms was closely similar: early presence in ganglion cell layer after which staining became restricted to Muller cells (particularly in the endfeet) and horizontal cell fibers in both rd1/rd1 and +/+. Doublets of alpha-GST and mu-GST were detected by Western blot analysis. Densitometry of these bands indicated steady reduction of alpha-GST content in rd1/rd1 retina starting from the second postnatal week. When alpha-GST and mu-GST were added exogenously to rd1/rd1 explants, photoreceptor rescue was produced that was more prominent in PN2 than in PN7 explants and more effective by alpha-GST than mu-GST. We propose that alpha-GST neuroprotection is mediated by reduction of tissue oxidative stress.
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| 6. |
- Axelsson, H E, et al.
(författare)
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Transient receptor potential vanilloid 1, vanilloid 2 and melastatin 8 immunoreactive nerve fibers in human skin from individuals with and without Norrbottnian congenital insensitivity to pain.
- 2009
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Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 162, s. 1322-1332
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Tidskriftsartikel (refereegranskat)abstract
- Transient receptor potential vanilloid 1 (TRPV1), vanilloid 2 (TRPV2) and melastatin 8 (TRPM8) are thermosensitive cation channels expressed on primary sensory neurons. In contrast to TRPV1, which is present on nociceptive primary afferents and keratinocytes in human skin, less is known about the distribution of TRPV2 and TRPM8 in this tissue. Immunohistochemistry of human forearm skin identified TRPV2 and TRPM8 immunoreactive nerve fibers in epidermis-papillary dermis and around blood vessels and hair follicles in dermis, although these nerve fibers were less abundant than TRPV1 immunoreactive nerve fibers throughout the skin. The TRPV2 and TRPM8 immunoreactive nerve fibers also showed immunoreactivity for calcitonin gene-related peptide (CGRP) and to a lesser extent substance P (SP). Neither of the TRP ion channels co-localized with neurofilament 200 kDa (NF200), vasoactive intestinal peptide (VIP) or tyrosine hydroxylase (TH). Nerve fibers immunoreactive for TRPV1, TRPV2, TRPM8, CGRP and SP were absent or substantially reduced in number in individuals with Norrbottnian congenital insensitivity to pain, an autosomal disease selectively affecting the development of C-fiber and Adelta-fiber primary afferents. Quantitative real time PCR detected mRNA transcripts encoding TRPV1 and TRPV2, but not TRPM8, in skin from healthy volunteers, suggesting that these ion channels are also expressed extraneuronally. In conclusion, nerve fibers in human skin express TRPV1, TRPV2 and TRPM8 that co-localize with the sensory neuropeptides CGRP and SP, but not with NF200, VIP or TH. A dramatic loss of such nerve fibers was seen in skin from individuals with Norrbottnian congenital insensitivity to pain, further suggesting that these ion channels are expressed primarily on nociceptive primary sensory neurons in human skin.
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| 10. |
- Bexell, Daniel, et al.
(författare)
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Characterization of the subventricular zone neurogenic response to rat malignant brain tumors
- 2007
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Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 147:3, s. 824-832
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Tidskriftsartikel (refereegranskat)abstract
- The subventricular zone (SVZ) is one of the neurogenic regions of the adult brain. We characterized the neurogenic response of the SVZ to the growth of brain tumors in the rat striatum. Abundant nestin positive cells, most likely representing reactive astrocytes, were found surrounding the tumor. However, we observed no substantial migration of nestin positive cells from the SVZ toward the tumor. Tumor growth resulted in decreased numbers of bromodeoxyuridine positive and Ki-67 positive proliferating cells and a concomitant increase in doublecortin and polysialylated neural cell adhesion molecule immunoreactivity within the SVZ. Neuroblasts were observed in high numbers in the area between the SVZ and the tumor, most likely pointing to the SVZ as the principal source of these cells. Neuroblasts located between the SVZ and the tumor expressed the transcription factor Pbx, a marker for immature striatal neurons. However, no evidence of neuroblast differentiation into fully mature neurons was found. This study thus demonstrates increased neuroblast immunoreactivity within the SVZ ipsilateral to a brain tumor in the striatum. SVZ-derived neuroblasts attracted by the tumor adopt an immature striatal phenotype indicating a region specific reparative mechanism in response to a malignant tumor. (C) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.
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