Investigating the role of retinoic acid in the vertebrate and invertebrate nervous system

Please consult the paper edition of this thesis to read. It is available on the 5th Floor of the Library at Call Number: Z 9999.5 B56 D64 2007

Although abundant in the developing central nervous system (CNS) of vertebrates, the precise roll of all-trans retinoic acid (RA) is neuronal development and regeneration is undetermined. This study suggests that all-trans RA acts via its RAR Beta receptor to stimulate neurite outgrowth from adult newt spinal cord explants, and may represent an important chemotropic molecule for nerve dependent lib regeneration. All-trans RA's effects are not limited to the vertebrate species, as it was found that all-trans RA induces neurite outgrowth and retains electrical excitability in isolated adult molluscan invertebrate neurons. Using analytical chemistry techniques, both all-trans RA and its isoform, 9-cis RA, were identified in the invertebrate CNS. 9-cis RA showed a similar neurotrophic role to that of all-trans RA on cultured molluscan neurons. Further, all-trans and 9-cis RA were capable of inducing growth cone chemoattraction. This occurred in the absence of the neuronal cell body, unlike the growth promoting and increased survival effects of all-trans RA, suggesting a novel signaling mechanism for all-trans RA in the invertebrate and vertebrate species. Investigating the factors involved in promoting neurite outgrowth may ultimately aid in designing strategies to prevent nerve degeneration and developing approaches to support axonal regeneration in humans.