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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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## Abstract

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. Toescu, Emil Colleges (2008 onwards) > College of Medical & Dental Sciences School of Clinical and Experimental Medicine R Medicine (General) University of Birmingham 3737
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