- Consequences of early-life stress for microglia throughout life
- Relevance for the hippocampus in aging and Alzheimer’s disease
- Award date
- 23 March 2018
- Number of pages
- Document type
- PhD thesis
- Faculty of Science (FNWI)
- Swammerdam Institute for Life Sciences (SILS)
Alzheimer’s disease (AD) is characterized by progressive cognitive decline and is one of the most common neurodegenerative diseases in elderly. The age-of-onset and progression of AD are modulated by environmental and/or lifestyle factors. Indeed, stress during the sensitive perinatal period elicits lasting effects on the adult brain and might en hance the risk for age-related cognitive decline, as well as AD itself.
In this thesis, we aimed to understand if exposure to stress in early-life (ES) lead to a stronger decline in cognition with aging and AD, and how this relates to neuropathology, neuroinflammation and neuroplasticity. We studied if 1) ES contributed to earlier onset or exacerbation of cognitive decline in old age and AD and 2) if ES accelerated or aggravated development of AD neuropathology as well as associated neuroinflammation and neuroplasticity. To answer these questions, we focused on different elements in the early-life brain, which can modulate the enduring consequences of ES.
The findings in this thesis provide evidence for ES mediated modulation of Aβ neuropathological progression in an AD model (APP/PS1 mice), while cognitive decline and neurogenesis were not aggravated by ES exposure in aging or in APP/PS1 mice. Furthermore, ES affected microglia and expression of various neuroinflammatory factors in both wild type and APP/PS1 mice. Such modulation potentially contributes to higher pro-inflammatory response upon immune activation, and to an ES-enhanced progression of AD neuropathology. These findings highlight the importance of future pre-clinical as well as clinical studies to further elucidate the relationship between ES and AD.
Thesis (complete) (Embargo up to and including 23 March 2020)
Chapter 3: Early-life stress mediated sensitization of the neuroinflammatory response to acute and chronic challenges (Embargo up to and including 23 March 2020)
Chapter 4: Early-life stress does not aggravate spatial memory or hippocampal neurogenesis in adult and middle-aged APP/PS1 mice (Embargo up to and including 23 March 2019)
Chapter 6: Early-life stress increases inter-individual variability in spatial memory performance, but does not alter hippocampal neurogenesis and neuroinflammation in aged mice (Embargo up to and including 23 March 2020)
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