| dc.contributor.author | Chiasson, Bernard Joseph. | en_US |
| dc.date.accessioned | 2014-10-21T12:37:09Z | |
| dc.date.available | 1995 | |
| dc.date.issued | 1995 | en_US |
| dc.identifier.other | AAINN08727 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/55082 | |
| dc.description | The studies in this thesis have examined the role of the immediate-early gene, c-fos, in brain function. The immediate-early genes (including members of the fos gene family) are among the first genes to be transcribed following neuronal excitation. The protein products of the immediate-early genes (IEGs) are transcriptional regulators which are believed to transduce neuronal stimuli into both short- and long-term transcriptional responses. Since constitutive expression of IEGs is low, and induced expression is transient, these genes have proved to be excellent targets for manipulation with antisense oligodeoxynucleotides (ODNs). We have examined the effects of phosphorothioate ODNs against c-fos on Fos induction in two model systems: acute Fos induction in the striatum following D-amphetamine treatment, and repeated Fos induction in the amygdala following electrical kindling (a model of epileptogenesis). We have demonstrated that single infusions of phosphorothioate (ODNs) were effective inhibitors of D-amphetamine-induced Fos expression. Unilateral inhibition of striatal Fos expression resulted in rotational behaviour indicating that Fos may play an important role in regulation of the basal ganglia. | en_US |
| dc.description | Repeated infusions of ODNs to the amygdala, which were necessary for kindling studies, were initially found to be cytotoxic. However, reducing the degree of sulfur substitutions in the backbone of the ODNs resulted in a loss of cytotoxicity without altering antisense activity. Animals kindled in the presence of antisense ODNs to c-fos required fewer stimuli to develop seizures when compared to a variety of control groups. These studies strongly suggest that c-fos is involved in the amygdala kindling process. Taken together the results suggest that the IEG c-fos may play a role in both the short- and long-term function of the brain. Overall, these findings demonstrate the considerable potential of antisense ODNs as research tools and potential therapeutic agents in neuroscience. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 1995. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Biology, Neuroscience. | en_US |
| dc.subject | Biology, Cell. | en_US |
| dc.title | Studies on the role ofc-fos in the mammalian brain: Application of antisense technology. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
