| dc.contributor.author | Shankar, L. Sai Latha. | en_US |
| dc.date.accessioned | 2014-10-21T12:33:55Z | |
| dc.date.available | 1999 | |
| dc.date.issued | 1999 | en_US |
| dc.identifier.other | AAINQ49291 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/55673 | |
| dc.description | This thesis describes an in vitro model established to study whether withdrawal of insulin, insulin-like growth factor-I (IGF-I) and serum causes apoptosis in oligodendroglial cells. In vitro, oligodendrocyte-type 2 astrocyte progenitor cells (O-2A) can develop into either an oligodendrocyte or a type-2 astrocyte. In the present study, O-2A progenitor cells derived from the rat cerebral cortex were differentiated into oligodendrocytes in the presence of insulin and IGF-I over 16 days. Antibodies to (O-2A) lineage specific developmental markers were used to characterize the cells. | en_US |
| dc.description | Placement of the cells into insulin, IGF-I and serum withdrawn media for 24h led to decreased numbers of intact nuclei and cells. The insulin and IGF-I deprived cells showed extensive process fragmentation but displayed intact cell bodies. Chromatin fluorescence of trophically deprived cells revealed nuclear stigmata typical of apoptosis. In situ nicked end labeling and gel electrophoresis revealed DNA fragmentation beginning at 6 h after insulin, IGF-I and serum withdrawal and peaking between 18 to 24 h. | en_US |
| dc.description | (--)-Deprenyl, a monoamine oxidase-B inhibitor markedly increased the survival of insulin, IGF-I and serum withdrawn oligodendrocytes. Experiments with general inhibitors of cytochrome P450 enzymes revealed (--)-desmethyldeprenyl as the active metabolite that mediated the anti apoptotic effects of (--)-deprenyl. The anti-apoptotic effects of (--)-desmethyldeprenyl was blocked by actinomycin and cycloheximide showing that (--)-desmethyldeprenyl required new protein synthesis for its anti-apoptotic action. (--)-Deprenyl and (--)-desmethyldeprenyl significantly increased the levels of myelin basic protein and proteolipid protein relative to that of insulin, IGF-I and serum withdrawn cells. (--)-Desmethyldeprenyl also prevented the decrease in mitochondrial membrane potential observed by insulin, IGF-I and serum withdrawal. These findings demonstrate for the first time that compounds like (--)-desmethyldeprenyl can maintain the survival of oligodendrocytes and their precursors in conditions of trophic insufficiency. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 1999. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Biology, Neuroscience. | en_US |
| dc.title | Oligodendrocyte apoptosis in vitro: Relationship to insulin and insulin-like growth factor-I withdrawal, new protein synthesis and mitochondrial membrane potential. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
