Sex-specific Effects of Maternal Separation on Cognition and LPS-induced Accumulation of Aβ in Adulthood
Peterman, J. L.1, White, J. D.1, Moore, H.1, Lopez, S. 1, Chumley, M. J.2 &Boehm, G. W.1 1Department of Psychology, Texas Christian University 2Department of Biology, Texas Christian University
Alzheimer's Disease (AD) is the most common form of dementia and the incidence is expected to drastically increase as our population grows older. AD is characterized by the accumulation of amyloid-beta (A) plaques and neurofibrillary tangles. Our laboratory has previously demonstrated that 7 consecutive daily injections of LPS (250 g/kg; i.p.) injections result in increased inflammation and significant elevation of amyloid-beta within the hippocampus of C57BL6/J mice. Given the relationship between stress, inflammation, and AD pathology onset and progression, we sought to explore how an early life stressor, maternal separation, could impact AD pathology 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/Saline injections and cognition was assessed utilizing the contextual fear conditioning (CFC) paradigm. Tissue was collected and hippocampal A levels were quantified via ELISA, and western blotting was utilized to explore potential mechanisms behind A alterations. Maternal separation significantly impaired cognitive function, and exacerbated LPS-induced accumulation of A in a sex-specific manner. Overall, the results suggest that early-life stress exacerbates inflammation-induced AD pathologies. Given that humans experience substantial daily stress throughout their lives, research into how early life stress can impact disease risk and development later in life is critical. Understanding how the interaction of stress and immune function may increase one's potential risk for AD, as well as impact disease pathology, is the first step in developing effective interventions. Understanding how the interplay between stress and inflammatory pathways function may increase one's potential risk for AD, and exacerbate impact disease pathogenesis, represents an important step in developing effective interventions.
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