Maternal Immune Activation Primes Deficiencies in Adult Hippocampal Neurogenesis

Amalie Couch, Thomas Berger, Bjørn Hanger, Rugile Matuleviciute, Deepak Srivastava, Sandrine Thuret, Anthony Vernon*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

14 Citations (Scopus)
47 Downloads (Pure)

Abstract

Neurogenesis, the process in which new neurons are generated, occurs throughout life in the mammalian hippocampus. Decreased adult hippocampal neurogenesis (AHN) is a common feature across psychiatric disorders, including schizophrenia, depression- and anxiety-related behaviours, and is highly regulated by environmental influences. Epidemiological studies have consistently implicated maternal immune activation (MIA) during neurodevelopment as a risk factor for psychiatric disorders in adulthood. The extent to which the reduction of hippocampal neurogenesis in adulthood may be driven by early life exposures, such as MIA, is however unclear. We therefore reviewed the literature for evidence of the involvement of MIA in disrupting AHN. Consistent with our hypothesis, data from both in vivo murine and in vitro human models of AHN provide evidence for key roles of specific cytokines induced by MIA in the foetal brain in disrupting hippocampal neural progenitor cell proliferation and differentiation early in development. The precise molecular mechanisms however remain unclear. Nonetheless, these data suggest a potential latent vulnerability mechanism, whereby MIA primes dysfunction in the unique hippocampal pool of neural stem/progenitor cells. This renders offspring potentially more susceptible to additional environmental exposures later in life, such as chronic stress, resulting in the unmasking of psychopathology. We highlight the need for studies to test this hypothesis using validated animal models of MIA, but also to test the relevance of such data for human pathology at a molecular basis through the use of patient-derived induced pluripotent stem cells (hiPSC) differentiated into hippocampal progenitor cells.
Original languageEnglish
Pages (from-to)410-422
Number of pages13
JournalBrain Behavior and Immunity
Volume97
Early online date29 Jul 2021
DOIs
Publication statusPublished - Oct 2021

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