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Short‐ and long‐term signatures of motherhood in the hippocampus: Implications for brain aging and dementia risk
Author(s) -
DuarteGuterman Paula,
Skandalis Dimitri A.,
Lieblich Stephanie E.,
Eid Rand S.,
Galea Liisa A.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.041311
Subject(s) - neuropathology , neuroinflammation , doublecortin , dementia , hippocampal formation , hippocampus , neuroplasticity , medicine , biology , endocrinology , psychology , neuroscience , disease , dentate gyrus
Background Diagnosis rates of Alzheimer’s disease (AD) are greater in women than men, who also show greater cognitive decline and AD neuropathology. Increasing parity (pregnancy and motherhood experience) is associated with reduced grey matter volume in the brain and in the long term greater risk of dementia, earlier age of AD onset, and AD neuropathology. This suggests that parity and AD are linked. The hippocampus is one of the first areas to be affected by AD. Here, we examine the short‐ and long‐term effects of parity on neuroplasticity and neuroinflammation to assess changes in hippocampal function, and apply transcriptomics to identify novel effects of parity on hippocampal physiology. Method Female rats were bred once (primiparous), twice (biparous), or not at all (nulliparous). Hippocampi were collected at 7 months (30 days postpartum) and 13 months (240 days postpartum) to measure synaptic density protein (PSD‐95 electrochemiluminescence assay), numbers of immature neurons (immunohistochemistry of doublecortin expression, DCX), neuroinflammation (IL‐1β, IL‐4, IL‐5, IL‐6, IL‐10, IL‐13, CXCL1, IFN‐γ, and TNF‐α electrochemiluminescence assay), and global gene expression (RNA sequencing). Results Synaptic protein PSD‐95 was significantly increased in mothers relative to nulliparous females but was independent of age. In contrast, DCX expression was reduced in mothers only at 7 months, and all groups exhibited significant reductions in DCX expression with age. Neuroinflammatory markers distinguished parity levels; for example, levels of interleukin‐6 (IL‐6) were elevated in biparous females of all ages. Finally, most differentially expressed genes in the transcriptome were associated with aging, but many transcripts were associated with parity exclusively at 7 months. Through gene ontology analysis, we found biological processes enriched during aging were especially involved in synaptic plasticity and neurogenesis, whereas parity involved metabolic processes and recycling of cellular components. Conclusion Our work identifies neuroplastic and neuroinflammatory signatures of parity in the hippocampus. The effects of motherhood are identified by short‐term physiological changes that persist through middle‐age. These data contribute to understanding the influence of parity on brain aging and Alzheimer’s risk.