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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Local dysfunction in cerebral cortex infiltrated by astrocytoma can cause epilepsy and focal neurological deficits, but the cellular pathology of peritumoral cortex remains poorly defined. The aims of the present study were to define the morphological changes which occur in neurons in tumor-infiltrated cerebral cortex, and to determine whether peritumoral neurons show expression of cell stress-related proteins. Archival specimens of diffuse astrocytoma (n = 28) were identified with areas of both tumor-infiltrated cortex and apparently non-infiltrated cortex. Immunohistochemistry was performed to structural neuronal proteins (MAP-2, neurofilament proteins), beta-amyloid precursor protein, growth associated protein-43 and to injury response proteins (poly(ADP-ribose) polymerase, poly(ADP-ribose), c-fos, and c-jun). Tumor-infiltrated cortex revealed neuronal loss and architectural disarray compared to non-infiltrated cortex. Pyramidal neurons showed thinning of the cytoplasmic rim and their neuritic processes showed increasing tortuosity, varicosity, fragmentation and loss, with axonal spheroid formation and dendritic beading. Poly(ADP-ribose) polymerase, poly(ADP-ribose) and c-fos were up-regulated in both infiltrated and non-infiltrated cortex, but c-jun expression was greater in areas of tumor-infiltrated cortex. Surviving neurons in cortex infiltrated by astrocytoma demonstrate, therefore, a sequence of morphological alterations in their dendritic, somatic and axonal compartments, and demonstrate a cell stress response. The patterns of cellular pathology identified suggest possible mechanisms, by which neurons are damaged and eventually lost in peritumoral brain.
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PMID:Morphological changes and stress responses in neurons in cerebral cortex infiltrated by diffuse astrocytoma. 1471 40

Identification of critical factors involved in oligodendroglial fate specification from endogenous neural stem cells is relevant to the development of therapeutic interventions that aim to promote remyelination. Here we report a novel role of the DNA repair protein poly-ADP-ribose polymerase-1 (PARP-1) in regulating the neural stem cell profile in the postnatal mouse forebrain subventricular zone (SVZ). We observed increased expression of Sox2 and Sox10 in the SVZ of postnatal day 11 (P11) PARP-1 knockout mice. This increase corresponded to increased Olig2 expression in Sox2-positive cells of the PARP-1 knockout mouse SVZ and decreased Map2abc expression compared with Sox2/Olig2 and Sox2/Map2abc expression in wild-type mice. We noted enhanced expression of proliferating oligodendrocyte progenitor cells (OPCs) at the expense of proliferating neuroblasts in the SVZ of PARP-1 knockout mice, by using Olig1/Ki67/DCX, NG2/Ki67/DCX, and PDGFR/BrdU/TuJ1 immunofluorescence labeling. In addition, the percentage of BrdU/Olig2 double-labeled cells increased in the SVZ and corpus callosum of PARP-1 knockout mice compared with wild-type mice. We also observed a decrease in DCX-positive cells without a decrease in the overall SVZ area in PARP-1 knockout mice, further indicating a switch from neuroblast to OPC fate. PARP-1 knockout mice displayed thinning of MBP expression in the corpus callosum and external capsule, suggesting that the enhanced OPC proliferation in the SVZ might compensate for deficiency in myelination. Together, our results show that PARP-1 deletion promotes SVZ neural stem cells toward a glial fate and suggest that future studies target PARP-1 as a potential therapeutic strategy for demyelinating diseases.
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PMID:PARP-1 deletion promotes subventricular zone neural stem cells toward a glial fate. 2243 11