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Title: Photobiomodulation in animal models of ageing and Alzheimer's disease
Author: Duggett, Natalie Amy
ISNI:       0000 0004 2735 0262
Awarding Body: Durham University
Current Institution: Durham University
Date of Award: 2013
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Photobiomodulation refers to low-intensity light therapy, utilising wavelengths in the near-infrared region of the electromagnetic spectrum to elicit biological effects. The principle aim of this investigation was to explore signalling pathways initiated by IR1072, with particular focus on heat shock proteins (HSPs), a family of proteins known to target cellular aggregates which are involved in the maintenance of cellular homeostasis. This was further examined by exploring the role of age and sex in the magnitude of biological effects induced. Another aim of this study was to explore the cytoprotective potential of IR1072 in conjunction with Alzheimer’s disease-related insults. The results of this study show chronic IR1072 exposure altered the expression of a number of HSPs in both CD-1 and TASTPM mice; including HSP105, HSP70, HSP27, and αB crystallin. The magnitude of effect differed with age and sex of CD-1 and TASTPM mice respectively; these differences coincided with altered endogenous activity of electron transport chain components. Acute exposure of CAD neuronal cultures provided significant neuroprotection against oxidative-stress and β-amyloid insults. Further characterisation of the CD-1 and TASTPM strains during ageing was established. CD-1 mice demonstrated reduced TARP γ2 with age, which may underlie learning deficits that become apparent during ageing. Chronic IR1072 exposure significantly increased TARP γ2 in 7 and 13 month old CD-1 mice, perhaps explaining improved working-memory reported following IR1072 exposure. Acute treatments of CD-1 mice altered Complex I and II activity in mitochondria. Chronic IR1072 exposure Caenorhabditis elegans was shown to consistently extend lifespan. This model system aided in establishing pathways essential for biological effects of IR1072, demonstrating the importance of HSF1 driven pathways, in particular those requiring HSP70. In conclusion, this research revealed mechanisms initiated by photobiomodulation at IR1072 that act to re-establish homeostasis, profoundly reduce amyloid load, prevent cell stress and cell death.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available