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Title: Control of gene expression in neurosecretory neurones
Author: Johnstone, Louise E.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1996
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This thesis examines mechanisms of regulation of neuropeptide gene expression in vivo in some neurosecretory hypothalamic neurones of the rat. In particular, the influence of neural pathways, acting via receptors and subsequent regulation of genetic transcription factors was measured and second messenger pathways were directly manipulated and the effects of their mutation on gene expression were measured. The magnocellular neurones of the supraoptic nucleus (SON) are known to be directly (i.e. non-synaptically) osmosensitive. Fos, the protein product of the immediate early gene c-fos, has been used as a marker of neuronal activation and its expression is induced in these neurones by increasing systemic hyperosmolarity. The effects of acute, direct hyperosmotic stimulation, via a microdialysis probe, on Fos expression in supraoptic nucleus magnocellular neurones was investigated. Fos expression was detected by immunohistochemistry (IHC). However, direct hyperosmotic stimulation failed to induce Fos expression in the magnocellular neurones in the SON but did induce Fox expression in glial cells within the SON and in the ventral glial lamina, as detected with double IHC. A receptor-mediated stimulus, cholecystokinin, applied directly to the SON did induce Fos expression in magnocellular neurones. These results indicate that Fos induction requires synaptically-mediated activation and consequent specific changes in cellular secondary messenger systems. Therefore Fos is not always induced when neurones are otherwise defined as active. In rats, chronic morphine administration into a lateral cerebral ventricle, over 5 days, results in the magnocellular oxytocin neurones developing dependence as demonstrated by the effects of administration of the opioid antagonist, naloxone, which results in their withdrawal excitation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available