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Title: Compartmentalisation of retinoic acid synthesis in neuronal cells, and the role of RA in the control of melatonin synthesis by the pineal gland
Author: Ransom, Jemma S.
ISNI:       0000 0004 2746 5588
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2012
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During embryogenesis, vitamin A metabolism to retinoic acid (RA) is tightly regulated in a precise spatiotemporal pattern. Aberrant retinoid signalling in the wrong place or at the wrong time has devastating consequences for development. Much is understood about the mechanisms by which at the level of specific tissues, RA synthesis from vitamin A is able to occur and activate target genes necessary for the developmental programme at any given stage. However, little is known about how retinoid transport and synthesis at the subcellular level occurs. Chapter 3 of this thesis investigates the subcellular compartments with which the vitamin A metabolising enzyme RALDH2 associates in embryonic neuronal cell lines. It is found that not only is RA synthesis tightly controlled by tissues, but that RA signalling within cells themselves may also be segmented. Aside from the importance of vitamin A during early development, it is now known that this dietary component is also vital in the maintenance of homeostasis during adulthood. This is particularly important for the adult CNS, where it is proposed that RA mediates hippocampal neurogenesis; hypothalamic neurogenesis; and physiological responses to seasonal changes in day length. The nocturnal hormone melatonin is a key signalling molecule relaying the length of the night to the rest of the brain and periphery, and by this means conveying information about the time of year. Vitamin A deficiency is known to severely reduce the amount of melatonin produced by the Quail pineal gland at night. Chapter 4 of this thesis investigates the circadian and circannual rhythms of retinoid genes such as the RALDH enzymes and retinoic acid receptors in both the SCN, and the pineal gland. RA is sufficient to increase the expression of the melatonin synthesising enzyme AANAT, and that this gene expression may be under the control of RALDH1.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Melatonin ; Vitamin A ; Tretinoin