Onset of Insulin Resistance in Hippocampal Synapses After Traumatic Brain Injury: Relevance to Alzheimer’s disease and Therapeutic Implications
| dc.creator | Franklin, Whitney | |
| dc.date.accessioned | 2021-04-30T19:36:15Z | |
| dc.date.created | 2019-05 | |
| dc.date.submitted | May 2019 | |
| dc.date.updated | 2021-04-30T19:36:18Z | |
| dc.description.abstract | Traumatic brain injury (TBI) is a risk factor for the later development of Alzheimer’s disease (AD), although the mechanisms contributing to this increased risk are unknown. Insulin resistance is an additional risk factor for AD whereby decreased insulin signaling increases synaptic sensitivity to amyloid beta (Aβ) and tau, thus contributing to the cognitive decline that characterizes this neurodegenerative disorder. Considering this, I used male Sprague-Dawley rats that underwent a lateral fluid percussion injury (FPI) at acute (2 and 7 days post-injury), intermediate (28 days post-injury), and chronic (3 months post-injury) time-points to investigate whether decreased insulin responsiveness in TBI animals is playing a role in synaptic vulnerability to AD pathology. I was able to detect acute and chronic decreases in insulin responsiveness in isolated hippocampal synaptosomes after TBI. In addition to assessing both Aβ and tau binding on synaptosomes, I performed electrophysiology at the intermediate and chronic time-points to assess the dysfunctional impact of Aβ and tau oligomers as well as the protective effect of insulin. While I found no difference in binding or degree of LTP inhibition by either Aβ or tau oligomers between sham and TBI animals, I did find that insulin treatment was able to block oligomer-induced LTP inhibition in sham animals but not in TBI animals. Since insulin treatment has been discussed as a therapy for AD, this gives valuable insight into therapeutic implications of treating AD patients based on a patient’s history of associated risk factors. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | https://hdl.handle.net/2152.3/11320 | |
| dc.subject | Insulin Resistance | |
| dc.subject | Synapses | |
| dc.subject | Traumatic Brain Injury | |
| dc.subject | Alzheimer's disease | |
| dc.title | Onset of Insulin Resistance in Hippocampal Synapses After Traumatic Brain Injury: Relevance to Alzheimer’s disease and Therapeutic Implications | |
| dc.type | Thesis | |
| dc.type.material | text | |
| local.embargo.lift | 2021-05-01 | |
| local.embargo.terms | 2021-05-01 | |
| thesis.degree.department | Neuroscience | |
| thesis.degree.grantor | The University of Texas Medical Branch at Galveston | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Neuroscience (Doctoral) |