Meeting Abstract
Studies of neurodegenerative disorders such as Alzheimers disease (AD) have long identified the cholinergic neurons as a site of dysfunction. Reduction in cortical acetylcholine (AChE) activity has been documented in patients with mild to moderate AD (Sabbagh and Cummings, 2011). Cholinergic abnormalities seen in AD also provide physiological targets that can be addressed with currently approved treatment options. In a collaborative effort with students of our summer Welch Program, we have designed putative acetylcholinesterase inhibitors whose efficacy are being tested using the regenerating model system, Lumbriculus variegatus. Acetylcholineesterase may also contribute to regeneration through its role in regulation of cell proliferation, differentiation, apoptosis and survival in non-neuronal cells (Fossati et al., 2013). Thus, the possible use of the cholinergic system during regeneration is intriguing. We have carried out initial studies to determine the effects of AChE on neural regeneration and recovery of function in our worm model system. We have determined the fission concentration where 50% of the population develops fission plans (FC50) and the lethal concentration where 50% of the population die (FC5) to be 0.0679mM and 2.3377mM respectively. Initial data suggests that this putative acetylcholinesterase inhibitor significantly reduces segmental regeneration in both the anterior and posterior regenerating worm fragments. It is therefore possible that acetylcholine may negatively regulate segmental regeneration L.variegatus.
