Chronic stress and Alzheimer’s disease (AD) both lead to degenerative changes in the hippocampus, a brain structure involved in episodic memory and regulation of the stress response. Mechanisms of aging (inflammation, oxidative stress, membrane damage, mitochondrial dysfunction, and insulin resistance) and a loss of brain-derived neurotrophic factor (BDNF), occur in cases of both stress-related depression and AD. Three studies were conducted using mouse models to determine whether exercise or treatment with an anti-aging multi-ingredient supplement (MDS) designed to counteract these aging mechanisms could protect the hippocampus, and associated behavioural functions, from either stress or AD. The first experiment revealed that the upregulation of neurogenesis by aerobic exercise in c57Bl/6 male mice does not occur after stress exposure. The MDS and exercise, but neither intervention alone, alleviated anhedonia, upregulated BDNF and increased neurogenesis.
The other two experiments evaluated whether the MDS could counteract a range of AD behavioural and biological manifestations in both sexes of the 3xTg-AD mouse model. At 3-4 months of age, 2 months of MDS-supplementation protected 3xTg-AD mice from developing deficits in working memory and spatial learning seen in vehicle-treated transgenic mice. The MDS continued to benefit 3xTg-AD females, but not males, on tests of 24-h recall under conditions of high interference until 11-12 months of age, along with upregulating hippocampal BDNF. The MDS also attenuated the splenomegaly seen in 3xTg-AD mice and normalized the previously undiscovered aberrant recruitment of CA1 and CA3 neurons by 3xTg-AD males during spatial encoding.
This work supports the use of diet and exercise to buffer against major depressive disorder (MDD) and AD in part by acting upon the hippocampus. It also recommends the use of lifestyle-based interventions to promote functional improvements in MDD or AD, and further elucidates the potential of BDNF and neurogenesis as therapeutic targets in counteracting these debilitating conditions. / Thesis / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/23413 |
| Date | January 2018 |
| Creators | Hutton, Craig P. |
| Contributors | Becker, Suzanna, Psychology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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