The focus of this thesis falls upon three different compounds (two related to cellular toxicity and one to cellular protection) and their effects in hippocampal culture. Aluminium (A1) is controversially associated with neurodegenerative diseases such as Alzheimer’s Disease (AD). Beta-amyloid (β A), the main constituent of senile plaques characteristic of AD, develops into its most toxic form upon aggregation with A1. Cannabidiol (CBD), on the other hand, is a non-psychotropic constituent of marijuana implicated as a potential neuroprotectant. The discovery of the endocannabinoid (e CB) system has dramatically accelerated the field of CB research. Intracellular Ca<sup>2+</sup> ([Ca<sup>2+</sup>]<sub>i</sub>) homeostasis and signalling in cultured hippocampal neurones were monitored using the Ca<sup>2+</sup>-sensitive fluorescent dye Fura-2 AM and microscopic time-lapse imaging techniques. Cell survival studies were conducted and visualised using cell-death markers with fluorescent and confocal laser scanning microscopy. The potencies of two novel organic Al citrate salts were ascertained and compared to an inorganic A1 (in HC1) solution. All treatments exerted toxicity in a dose-dependent manner within the concentration range tested, with neurones exhibiting greater sensitivity than glia. Since Al facilitates βA aggregation, the two were applied in combination, however, they did not demonstrate obviously facilitated responses compared to individual application. CBD induced a clear [Ca<sup>2+</sup>]<sub>I</sub> rise that partially required L-type voltage-gated Ca<sup>2+</sup> channels and release from intracellular stores, possibly via ryanodine receptor-regulated Ca<sup>2+</sup>-induced Ca<sup>2+</sup> release. The CBD response was independent of antioxidant, phospholipase C and characteristic CB receptor pathways, however, their blockade facilitated the response, suggesting that an endogenous CB tone exists, to which the CBD mechanism may be negatively coupled.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:419658 |
| Date | January 2005 |
| Creators | Drysdale, Alison Jayne |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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