Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/30777
Title: Long term effect of nicotinic acetylcholine receptor activation and downstream signalling in neurons
Authors: Ziviani, Elena
Award date: 2005
Presented at: University of Leicester
Abstract: Nicotinic acetylcholine receptors (nAChRs) are widely present in the central nervous system (CNS). However, their cellular functions and physiological significance are not yet fully understood. Recently, in vivo and in vitro studies have suggested a possible neuroprotective role for nAChRs. Exposure to nicotine, an agonist at nAChRs, has been shown to protect from neurotoxicity induced by NMDA, glutamate and potassium withdrawal, and to prevent beta-amyloid induced neurotoxicity. Furthermore, stimulation of nAChRs has been shown to delay the ageing process of nigrostriatal neurons, increase neurotrophic factor levels and up-regulate the expression of NGF receptors in the brain. These observations may provide a basis for the findings that cigarette smoking is negatively correlated with Parkinson's disease and positively correlated with the delayed onset of Alzheimer's disease (AD). In conjunction with this, nicotine has been shown to affect a wide variety of biological functions including gene expression.;As nAChRs are calcium permeable channels, we have focused this current study on the effect of nicotine on the regulation of cellular proteins responsible for calcium-mobilisation, -transportation and -buffering. We found that in cortical neurons treated with 10microM nicotine for 24 h there is a selective up-regulation of ryanodine receptor 2 (RyR2), a calcium release channel present in the endoplasmic reticulum. In contrast, the expression of the other calcium-transporting and calcium-binding proteins tested were not affected. In nicotine treated cortical neurons, the increase RyR number was mirrored by a significant modification of the calcium response upon ryanodine stimulation.;In conclusion, our data show for the first time the effect of nicotine on the expression of proteins involved in calcium homeostasis.
Links: http://hdl.handle.net/2381/30777
Type: Thesis
Level: Doctoral
Qualification: PhD
Rights: Copyright © the author. All rights reserved.
Appears in Collections:Theses, MRC Toxicology Unit
Leicester Theses

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