Early and late effects of maternal experience on hippocampal neurogenesis, microglia, and the circulating cytokine milieu

Neurobiol Aging. 2019 Jun:78:1-17. doi: 10.1016/j.neurobiolaging.2019.01.021. Epub 2019 Feb 2.


The maternal brain displays considerable plasticity, and motherhood is associated with changes in affective and cognitive function. Motherhood can alter the trajectory of brain aging, including modifications to neuroplasticity and cognition. Here, we investigated the short- and long-term effects of motherhood on hippocampal neurogenesis, microglial density and morphology, and circulating cytokines, domains known to be altered with age and implicated in cognition and mood. Female rats were bred then euthanized during gestation or at various postpartum time points, culminating in middle age, and nulliparous rats served as age-matched controls. Hippocampal neurogenesis was significantly suppressed during gestation and the postpartum period. Interestingly, neurogenesis declined significantly in middle-aged nulliparous rats but increased in primiparous rats across the same period. Transient postpartum adaptations to the neuroimmune environment of the hippocampus were evidenced, as Iba-1-immunoreactive microglia assumed a deramified morphology followed by increased density. Intriguingly, aging-related changes in circulating cytokines were dependent on parity. These adaptations in neurogenic and immune processes may have ramifications for maternal mood and cognition across the peripartum period and beyond.

Keywords: Anti-inflammatory cytokines; Cell proliferation; Doublecortin; Iba-1; Ki67; Middle age; Motherhood; Neurogenesis; Postpartum; Pregnancy; Proinflammatory cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Affect
  • Aging* / immunology
  • Aging* / metabolism
  • Aging* / pathology
  • Aging* / physiology
  • Animals
  • Calcium-Binding Proteins
  • Cell Count
  • Cognition
  • Cytokines / metabolism*
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Female
  • Hippocampus / immunology
  • Hippocampus / physiology*
  • Humans
  • Male
  • Microfilament Proteins
  • Microglia / pathology
  • Microglia / physiology*
  • Microtubule-Associated Proteins
  • Mothers* / psychology
  • Neurogenesis / physiology*
  • Neuroimmunomodulation
  • Neuropeptides
  • Postpartum Period / physiology
  • Postpartum Period / psychology
  • Pregnancy
  • Rats, Sprague-Dawley


  • Aif1 protein, rat
  • Calcium-Binding Proteins
  • Cytokines
  • Dcx protein, rat
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Microfilament Proteins
  • Microtubule-Associated Proteins
  • Neuropeptides