Kaila Tonge

Year

2017

Degree Name

BSci Hons

Department

School of Earth & Environmental Sciences

Advisor(s)

Anthony Dosseto

Abstract

Metal dyshomeostasis in the brain is an underlying feature of Alzheimer’s disease. The further understanding of metal distribution in the brain is critical to further explore the role of metals in AD. The specific causes and effects that result in metals influencing the build-up of toxic, insoluble amyloid-beta plaques remain ambiguous. Treatment of cannabidiol (CBD) to APPxPS1 mice has been studied to prevent social recognition deficit and has the potential for a preventative treatment for Alzheimer’s disease (AD). This project analyses the distribution of Cu, Zn and Fe in healthy and affected transgenic APPxPS1 mice brains and produces comprehensive metal concentration maps outlining any accumulations and/or trends emerging. This project studies how metal distribution is affected when transgenic mice with Alzheimer’s and wild-type (WT), healthy mice are treated with cannadibiol. Four groups of mice will be studied for comparison consisting of 14 APPxPS1 mice exhibiting AD (7 treated with CBD and 7 untreated) and 16 wild-type, healthy mice (8 treated with CBD and 8 untreated). The thirty sample mice brains were prepared and cryosectioned and analysed using laser ablation inductively coupled plasma mass spectrometry where metal concentrations were quantified using matrix-matched standards. Metal distribution maps were created and spatial analysis conducted to compare areas of metal deficiency or accumulation between the four groups. The metal concentration maps highlighted trends for each metal in the brain, such as Zn enrichment in the corpus callosum. The hippocampus and cerebellum are identified as regions with enhanced plaque pathology and average concentrations of metals between these regions were compared. These areas can indicate potential regions of increased (or decreased) metal activity which could be the result of failed mechanisms to control metal ion homeostasis. The comparison of metal concentrations in the whole brain, hippocampus and cerebellum of APPxPS1 with AD to WT mice identified a lower average concentration of metals in an AD brain. Treatments of CBD to both APPxPS1 mice and WT mice resulted in a higher metal concentration on average. Therefore, it is indicated that metals in AD affected brains are deficient and metal-targeting treatments, such as metal chelators, could prove to be therapeutic for AD. The treatment of CBD was found to increase the average metal concentration in WT brains to much higher levels which could potentially lead to toxicity. The findings in this study pave the way for future research to further explore metal deficiency in AD and treatments specifically targeting metals. The treatment of CBD can also be further explored in both its therapeutic heightening of metal concentrations in an AD brain and its potentially damaging heightening of metal concentrations in WT.

FoR codes (2008)

1109 NEUROSCIENCES, 110903 Central Nervous System

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Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.