Effects of maternal separation on Alzheimer's Disease-related pathology in adult C57BL/6J miceShow full item record
Title | Effects of maternal separation on Alzheimer's Disease-related pathology in adult C57BL/6J mice |
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Author | Peterman, Julia Lauren |
Date | 2020 |
Genre | Dissertation |
Degree | Doctor of Philosophy |
Abstract | Alzheimer¿s Disease (AD) is the most common form of dementia, with an incidence expected to drastically increase as our population grows older. AD is characterized by the accumulation of amyloid-beta (AB) plaques and neurofibrillary tangles. Our laboratory has previously demonstrated that 7 consecutive daily injections of LPS (250 ug/kg; i.p.) result in increased inflammation and significant elevation of amyloid-beta within the hippocampus of C57BL/6J mice. Given the relationship between stress, inflammation, and AD pathology, we sought to explore how an early life stressor, maternal separation (MS), could impact AD-like markers in adulthood. Mouse pups were separated from their mothers for three hours daily from post-natal day 2 (PND2) to PND21 and then were allowed to age in standard housing conditions into adulthood. At 4-6 months of age, mice received LPS or Saline injections and cognition was assessed utilizing a contextual fear conditioning (CFC) and open field paradigms. Tissue was collected and hippocampal AB levels were quantified via ELISA, while western blotting was utilized to explore potential mechanisms behind AB alterations. Maternal separation significantly impaired cognitive function in CFC and resulted in decreased hippocampal BDNF expression in males and females. MS also exacerbated LPS-induced accumulation of AB in females, and increased hippocampal BACE1 expression in male mice. MS also altered anxiety behavior in open field in a sex-specific manner. Overall, the results suggest that early-life stress can exacerbate inflammation-induced AD-like pathologies in adulthood. Understanding how the interaction of stress and immune function may increase one¿s potential risk for AD, as well as impact AD pathogenesis, are some of the first steps in developing effective interventions. |
Link | https://repository.tcu.edu/handle/116099117/39868 |
Department | Psychology |
Advisor | Boehm, Gary W. |
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- Doctoral Dissertations [1525]
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