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1.  HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain 
Pain  2013;154(9):1668-1679.
Summary
Intrathecal delivery of histone deacetylase inhibitors ameliorates hypersensitivity in models of neuropathic pain. This effect may be mediated at the level of the spinal cord through inhibition of HDAC1 function.
Histone deacetylase inhibitors (HDACIs) interfere with the epigenetic process of histone acetylation and are known to have analgesic properties in models of chronic inflammatory pain. The aim of this study was to determine whether these compounds could also affect neuropathic pain. Different class I HDACIs were delivered intrathecally into rat spinal cord in models of traumatic nerve injury and antiretroviral drug–induced peripheral neuropathy (stavudine, d4T). Mechanical and thermal hypersensitivity was attenuated by 40% to 50% as a result of HDACI treatment, but only if started before any insult. The drugs globally increased histone acetylation in the spinal cord, but appeared to have no measurable effects in relevant dorsal root ganglia in this treatment paradigm, suggesting that any potential mechanism should be sought in the central nervous system. Microarray analysis of dorsal cord RNA revealed the signature of the specific compound used (MS-275) and suggested that its main effect was mediated through HDAC1. Taken together, these data support a role for histone acetylation in the emergence of neuropathic pain.
doi:10.1016/j.pain.2013.05.021
PMCID: PMC3763368  PMID: 23693161
Histone deacetylase; Histone deacetylase inhibitors; Neuropathic pain
2.  Schwann cell-specific JAM-C-deficient mice reveal novel expression and functions for JAM-C in peripheral nerves 
The FASEB Journal  2012;26(3):1064-1076.
Junctional adhesion molecule-C (JAM-C) is an adhesion molecule expressed at junctions between adjacent endothelial and epithelial cells and implicated in multiple inflammatory and vascular responses. In addition, we recently reported on the expression of JAM-C in Schwann cells (SCs) and its importance for the integrity and function of peripheral nerves. To investigate the role of JAM-C in neuronal functions further, mice with a specific deletion of JAM-C in SCs (JAM-C SC KO) were generated. Compared to wild-type (WT) controls, JAM-C SC KO mice showed electrophysiological defects, muscular weakness, and hypersensitivity to mechanical stimuli. In addressing the underlying cause of these defects, nerves from JAM-C SC KO mice were found to have morphological defects in the paranodal region, exhibiting increased nodal length as compared to WTs. The study also reports on previously undetected expressions of JAM-C, namely on perineural cells, and in line with nociception defects of the JAM-C SC KO animals, on finely myelinated sensory nerve fibers. Collectively, the generation and characterization of JAM-C SC KO mice has provided unequivocal evidence for the involvement of SC JAM-C in the fine organization of peripheral nerves and in modulating multiple neuronal responses.—Colom, B., Poitelon, Y., Huang, W., Woodfin, A., Averill, S., Del Carro, U., Zambroni, D., Brain, S. D., Perretti, M., Ahluwalia, A., Priestley, J. V., Chavakis, T., Imhof, B. A., Feltri, M. L., Nourshargh, S. Schwann cell-specific JAM-C-deficient mice reveal novel expression and functions for JAM-C in peripheral nerves.
doi:10.1096/fj.11-196220
PMCID: PMC3370675  PMID: 22090315
adhesion molecules; tight junctions; peripheral nerves
3.  The spatiotemporal localization of JAM-C following sciatic nerve crush in adult rats 
Brain and Behavior  2012;2(4):402-414.
JAM-C is a junctional adhesion molecule, enriched at tight junctions on endothelial and epithelial cells, and also localized to Schwann cells at junctions between adjoining myelin end loops. The role of JAM-C following peripheral nerve injury (PNI) is currently unknown. We examined the localization of JAM-C after sciatic nerve crush injury in adult rats. JAM-C immunoreactivity was present in paranodes and incisures in sham surgery control nerve, but distal to the crush injury significantly decreased at three and 14 days. JAM-C was re-expressed at 28 days and, by 56 days, was significantly increased in the distal nerve compared to controls. In a 7-mm length of sciatic nerve sampled distal to the crush site, the densities of JAM-C immunoreactive paranodes increased in the distal direction. Conversely, the densities of JAM-C immunoreactive incisures were highest immediately distal to the crush site and decreased in the more distal direction. Further analysis revealed a strong correlation between JAM-C localization and remyelination. Fifty-six days after crush injury, greater densities of JAM-C paranodes were seen compared to the nodal marker jacalin, suggesting that paranodal JAM-C precedes node formation. Our data are the first to demonstrate a potential role of JAM-C in remyelination after PNI.
doi:10.1002/brb3.63
PMCID: PMC3432963  PMID: 22950044
JAM-C; paranodes; peripheral nerve injury; remyelination; Schwann cells
4.  Comparative analysis of the time-dependent functional and molecular changes in spinal cord degeneration induced by the G93A SOD1 gene mutation and by mechanical compression 
BMC Genomics  2008;9:500.
Background
Mutations of the superoxide dismutase 1 (SOD1) gene are linked to amyotrophic lateral sclerosis (ALS), an invariably fatal neurological condition involving cortico-spinal degeneration. Mechanical injury can also determine spinal cord degeneration and act as a risk factor for the development of ALS.
Results
We have performed a comparative ontological analysis of the gene expression profiles of thoracic cord samples from rats carrying the G93A SOD1 gene mutation and from wild-type littermates subjected to mechanical compression of the spinal cord. Common molecular responses and gene expression changes unique to each experimental paradigm were evaluated against the functional development of each animal model. Gene Ontology categories crucial to protein folding, extracellular matrix and axonal formation underwent early activation in both experimental paradigms, but decreased significantly in the spinal cord from animals recovering from injury after 7 days and from the G93A SOD1 mutant rats at end-stage disease. Functional improvement after compression coincided with a massive up-regulation of growth-promoting gene categories including factors involved in angiogenesis and transcription, overcoming the more transitory surge of pro-apoptotic components and cell-cycle genes. The cord from G93A SOD1 mutants showed persistent over-expression of apoptotic and stress molecules with fewer neurorestorative signals, while functional deterioration was ongoing.
Conclusion
this study illustrates how cytoskeletal protein metabolism is central to trauma and genetically-induced spinal cord degeneration and elucidates the main molecular events accompanying functional recovery or decline in two different animal models of spinal cord degeneration.
doi:10.1186/1471-2164-9-500
PMCID: PMC2585103  PMID: 18947433
5.  Synthesis and Biological Evaluation of Ezetimibe Analogs as Possible Cholesterol Absorption Inhibitors 
In order to investigate the SAR of Ezetimibe analogs for cholesterol absorption inhibitions, amide group and electron-deficient pyridine ring were introduced to the C-(3) carbon chain of Ezetimibe. Eight new derivatives of the 2-azetidinone cholesterol absorption inhibitors have been synthesized, and all of them were enantiomerically pure. All the new compounds were evaluated for their activity to inhibit cholesterol absorption in hamsters, and most of them showed comparable effects in lowering the levels of total cholesterol in the serum.
doi:10.2174/157018011795906776
PMCID: PMC3179128  PMID: 21966284
2-Azetidinone derivatives; Enantiomerically pure; Cholesterol absorption inhibition.

Results 1-5 (5)