Investigating the effects of aging and the neuromodulator retinoic acid on neurite outgrowth in a novel CNS organ culture
Neurite outgrowth is a critical process for nervous system regeneration following injury. However, aging impairs this process through changes in calcium handling, neurotransmitter sensitivity, and energy metabolism. In this thesis, I investigated agerelated changes in neurite outgrowth using a novel central nervous system (CNS) organ culture, in which outgrowth can be observed from cut nerves resting on the surface of culture media. I demonstrated how aging significantly reduces the ability of the CNS to initiate outgrowth and that individual nerves differ in their regenerative capacity, exhibiting either vulnerability or resilience to age-related decline. Further, I explored the effects of retinoic acid, a vitamin A metabolite that influences neurite outgrowth. Retinoic acid promoted outgrowth in the CNS from young animals but not aged animals, and high concentrations of retinoic acid impaired outgrowth at all ages. These findings provide new insights into age-related deficits in neurite outgrowth and their modulation by retinoic acid signaling.
NATURAL SCIENCES::Biology::Cell and molecular biology::Neurobiology
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