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dc.creatorComerota, Michele
dc.date.accessioned2018-11-16T17:17:24Z
dc.date.available2018-11-16T17:17:24Z
dc.date.created2018-08
dc.date.submittedAugust 2018
dc.identifier.urihttps://hdl.handle.net/2152.3/10725
dc.description.abstractAlzheimer’s Disease (AD) is a multifactorial neurodegenerative dementia with no curative therapeutic options. One of the earliest impairments in AD triggering cognitive decline is the synaptic dysfunction induced by the selective targeting and interruption of the synaptic region by the small oligomeric form of amyloid beta (Aβ). Recently, the co-presence of Aβ oligomers (Aβo) and tau oligomers (tau-o) at the synapses has been suggested to exacerbate this dysfunction. Therefore, the development of therapeutics aimed at protecting the synapses from the toxic binding of both proteins at the synapses can preserve synaptic health and cognitive function. With this goal in mind, the present study investigated the transcranial application of near infrared light (NIR, 600-1000 nm) as a potential treatment for AD. The primary objective of this project was to determine the effect of NIR light treatments (670 nm; 90 sec/day for 4 weeks) on the dysfunctional synaptic impact of oligomers. To achieve this goal, we investigated the modulation of the synaptic Aβo and tau-o load, the susceptibility of synapses to Aβo and tau-o binding and the resulting impaired long-term potentiation (LTP). We also investigated multiple mechanisms induced by NIR light. We found a significant reduction of Aβ1-42 at the synapses of NIR light treated APP transgenic (Tg2576) and 3xTg-AD mice. Further, 3xTg-AD and htau mice had reduced tau oligomers at the synapses and in the total protein extract after NIR light treatment. We further found a reduction in ex vivo synaptic Aβo binding and Aβo induced depressed LTP in wild type mice treated with NIR light while tau-o binding and resulting depressed LTP was not changed. In addition, we found increased efficiency of synaptic mitochondria, an upregulation of autophagy and increased inducible heat shock protein 70 (HSP70) levels in the synapses of NIR light treated mice suggesting mechanisms contributing to NIR light induced synaptic protection and clearance of the toxic proteins. Collectively, these results support NIR light as a viable treatment option for AD by promoting the reduction of Aβ and tau pathology, as well as, synaptic resistance to Aβ oligomer binding thus alleviating the ensuing synaptic impairments.
dc.format.mimetypeapplication/pdf
dc.subjectAlzheimer's disease, near infrared light, amyloid beta oligomers, tau oligomers
dc.titleNear infrared light to promote synaptic resilience to Alzheimer’s Disease neuropathology
dc.typeThesis
dc.date.updated2018-11-16T17:17:25Z
dc.type.materialtext
thesis.degree.nameNeuroscience (Doctoral)
thesis.degree.levelDoctoral
thesis.degree.grantorThe University of Texas Medical Branch at Galveston
thesis.degree.departmentNeuroscience


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