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Neuronal dendropathy in CNS degeneration: A new marker for protection and recovery

Bevan, Ryan 2020. Neuronal dendropathy in CNS degeneration: A new marker for protection and recovery. PhD Thesis, Cardiff University.
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Abstract

Neuronal dendritic and synaptic degeneration are early markers of neurodegeneration occurring in the brain of Alzheimer’s disease (AD). AD is the most common type of dementia characterised by the accumulation of extracellular amyloid plaques and neurofibrillary tangles, accompanied by neuroinflammation leading to neurodegeneration. AD diagnosis is often complex, expensive and/ or invasive, and only detect late stages of pathological changes. The retina, an extension of the central nervous system (CNS), develops AD-like pathology and may reflect ongoing pathological changes in the AD brain. Retinal ganglion cells (RGCs), the output neurons of the retina, are vulnerable to degeneration and may offer as a potential target for detecting and monitoring AD pathology. However, it is unclear whether RGC degeneration is a consistent feature in the AD retina. This thesis utilises DiOlistic labelling to investigate RGC dendritic pruning and hippocampal dendritic spine loss in the AD mouse models and assesses the impact of immune system modulation via deficiency of the complement system, elevated systemic inflammation (bacterial and viral) and dietary modulation (high fat diet and probiotics). All AD mouse models (Tg2576, 3xTg-AD and APPN-G-F) displayed excessive RGC dendritic pruning that occurred contemporaneously with dendritic spine loss in the hippocampus. In the 3xTg-AD model, deficiency in the complement system offered neuroprotection against both RGC dendritic and hippocampal synaptic pruning whilst elevated systemic inflammation (bacterial and viral) and high fat dietary modulation exacerbated neurodegeneration. Probiotic dietary supplementation was also associated with synaptic protection in the hippocampus. Overall, this thesis demonstrates that excessive RGC dendritic pruning is a common feature in the retina of AD mouse models and occurs at the time of ongoing synaptic loss in the hippocampus. These findings support the prospective use of retinal analysis to monitor AD progression and severity, providing an accessible measure that reflects pathology within the brain.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Optometry and Vision Sciences
Subjects: R Medicine > RE Ophthalmology
Uncontrolled Keywords: Alzheimer’s disease, Retinal ganglion cells, Dendritic spines, DiOlistic labelling, Sholl analysis, Synaptic pruning, Complement system, Systemic Inflammation, Probiotics.
Date of First Compliant Deposit: 5 February 2021
Last Modified: 05 Feb 2021 10:55
URI: https://orca.cardiff.ac.uk/id/eprint/138256

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