Investigating Synergistic Effects of Mild Traumatic Brain Injury and Reduced Cholinergic Tone on Attentional Deficits and Alzheimer's-Like Pathology in hAβ and hTau mice
Abstract
Mild traumatic brain injury (mTBI) increases the risk of Alzheimer’s disease. The early cholinergic decline in Alzheimer’s disease and cholinergic damage observed after TBI suggest a distinct role of this neural system in vulnerability to Alzheimer’s disease following TBI. This thesis evaluated the role of repetitive mTBI and cholinergic dysfunction in the development of cognitive deficits, specifically attentional deficits, and Alzheimer’s-related pathology in mice expressing humanized amyloid-beta and tau and a vesicular acetylcholine transporter knockdown to induce a mild cholinergic deficit. Using the rodent continuous performance test, it was shown that repetitive mTBI in the presence of an already vulnerable cholinergic system induced chronic, sex-specific attentional impairments. However, repetitive mTBI and cholinergic dysfunction alone did not induce significant deficits. Injured cholinergic deficient mice also exhibited an increase in degenerative hippocampal granules. These findings indicate the synergistic role of cholinergic dysfunction and mTBI in the development of behavioural deficits with aging.