Isanski, Barbara Anna
(2007)
Interactions of cholinergic innervation and soluble Aβ42 peptide metabolism in the hippocampus.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Alzheimer's Disease (AD) is a chronic neurodegenerative disorder characterized clinically by dementia and neuropathologically by the presence of amyloid-β (Aβ) plaques, neurofibrillary tangles, and neuronal and synapse loss. AD dementia severity correlates with reductions in synapses as well as in cholinergic markers, including choline acetyltransferase (ChAT) and acetylcholine esterase (AChE). However, the exact relationship of these changes with Aβ metabolism and plaques is unclear. Recently, it has been proposed that reduced cholinergic activity can increase levels of Aβ peptide. We investigated this relationship using a well-characterized model of hippocampal cholinergic denervation (achieved by fimbria-fornix transection) in a unique human Aβ "knock-in" mouse model of AD. The fimbria fornix lesion was effective in diminishing the cholinergic input to the hippocampus; ChAT immunoreactive fiber densities were reduced in the hippocampus, and cholinergic enzyme activity levels were reduced by almost 50% compared to naïve animals. Fimbria fornix lesions also resulted in a 3-fold increase in soluble Aβ42 over naives, supporting the hypothesis that loss of cholinergic innervation increases Aβ peptide levels in target fields. Our data indicate that cholinomimetic therapies could prove valuable in suppressing increases in potentially neurotoxic soluble Aβ levels, and provide a model for evaluating in vivo the relationship between cholinergic function and amyloid metabolism.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
19 December 2007 |
| Date Type: |
Completion |
| Defense Date: |
14 December 2007 |
| Approval Date: |
19 December 2007 |
| Submission Date: |
19 December 2007 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Neurobiology |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Alzheimer's Disease; amyloid-β; fimbria fornix lesion |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-12192007-000351/, etd-12192007-000351 |
| Date Deposited: |
10 Nov 2011 20:11 |
| Last Modified: |
15 Nov 2016 13:54 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/10433 |
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