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Age dependent changes in neuronal vulnerability and its metabolic substrates

Chitolie, Mark Stephen (2012)
M.Phil. thesis, University of Birmingham.

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Ageing is an important biological issue affecting all organs in the body. Following from earlier suggestions that the primary neuronal cultures could be aged \(in\) \(vitro\), the first aim of this project was to define the survival and vulnerability of cultured cerebellar granule neurones maintained in culture for < 60 days. Although there was an age-dependent decrease in neuronal number, the remaining neurons were viable. Using this ‘ageing in a dish model’ as a possible \(in\) \(vitro\) model, the project then assessed the age-dependent changes in neuronal vulnerability, particularly in response to glutamatergic stimulation. Overall, with age in culture, there was an increased sensitivity to glutamate that was associated with a larger Ca\(^2\)\(^+\) influx and a greater level of Ca\(^2\)\(^+\) sequestration by the mitochondria. The size of the mitochondrial Ca\(^2\)\(^+\) load was dependent not only upon the amplitude of the Ca\(^2\)\(^+\) signal but also on the length of time that the cytosolic Ca\(^2\)\(^+\) ([Ca\(^2\)\(^+\)]i) remained elevated. Providing that sufficient time was allowed, the mitochondria retained, even in the older neurones, their ability to recover from the elevated Ca\(^2\)\(^+\). This work provides more insight into the underlying mechanisms which contribute to the increase in neuronal vulnerability during the ageing process.

Type of Work:M.Phil. thesis.
Supervisor(s):Toescu, Emil
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine
Subjects:R Medicine (General)
Institution:University of Birmingham
ID Code:3737
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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