| Autor: |
Lee, Bonnie H, Duarte‐Guterman, Paula, Lieblich, Stephanie E, Ibrahim, Muna, Eid, Rand S, Wen, Yanhua, Cevizci, Mel, Galea, Liisa A |
| Zdroj: |
Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2022 Supplement 4, Vol. 18 Issue 4, p1-1, 1p |
| Abstrakt: |
Background: Females have a greater lifetime risk of Alzheimer's disease (AD) compared to males, differences which are further exacerbated with possession of APOEe4 alleles, the greatest genetic risk factor for sporadic AD. Although studying sex and gender differences is important, so is studying sex‐linked factors such as parity (pregnancy and motherhood). Previous parity influences brain aging trajectories in both humans and rodents and may be associated with a greater risk of AD and greater neuropathology. Neuroinflammation is increased with AD, reduces hippocampal neurogenesis, and activates the tryptophan‐kynurenine pathway (TKP), and all these factors are influenced by aging and parity. We investigated whether previous parity influences neuroinflammation and neuroplasticity in middle‐aged rats, dependent on APOEe4 genotype. Method: Age‐matched wildtype (WT) and humanized (h) APOEe4e4 knock‐in female rats were nulliparous (never mothered) or primiparous (first‐time mothers). Middle‐age (13‐14 months old) rats were euthanized to examine markers of hippocampal neuroinflammation (microglia and cytokine signalling) and neurogenesis. Result: In line with previous research, wildtype primiparous rats had greater levels of neurogenesis than nulliparous rats – however, the reverse was true in hAPOEe4 rats, as hAPOEe4 primiparous rats had lower levels of neurogenesis than hAPOEe4 nulliparous rats in the ventral hippocampus. Perhaps paradoxically, hAPOEe4 primiparous rats had fewer microglia and less proinflammatory cytokine expression (IL‐l1β, IFNγ, TNFα) than wildtype primiparous rats in the ventral hippocampus. Conclusion: These findings indicate that past reproductive experience and APOEe4 genotype need to be considered in aging and Alzheimer's disease research. [ABSTRACT FROM AUTHOR] |
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