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Maternal Immune Activation Primes Deficiencies in Adult Hippocampal Neurogenesis

Research output: Contribution to journalReview articlepeer-review

Original languageEnglish
Pages (from-to)410-422
Number of pages13
JournalBrain Behavior and Immunity
Volume97
Early online date29 Jul 2021
DOIs
E-pub ahead of print29 Jul 2021
PublishedOct 2021

Bibliographical note

Funding Information: AC: conception and design, literature searching, manuscript writing. TB, BH and RM: manuscript writing and editing. DPS and ST: manuscript writing, editing and financial support. AV: conception and design, manuscript writing, financial support, final approval of manuscript. AC, DPS and ACV acknowledge financial support for this study from the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/S001506/1). The work (at King’s College, London) was also supported by the Medical Research Council (MRC) Centre grant (MR/N026063/1). TB is in receipt of a PhD studentship funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. ST’s lab is partly funded by MRC research grants MR/N030087/1 and MR/S00484X/1. RM is in receipt of the MRC-Sackler PhD Programme studentship as part of the MRC Centre for Neurodevelopmental Disorders (Medical Research Council MR/P502108/1). Funding Information: AC: conception and design, literature searching, manuscript writing. TB, BH and RM: manuscript writing and editing. DPS and ST: manuscript writing, editing and financial support. AV: conception and design, manuscript writing, financial support, final approval of manuscript. AC, DPS and ACV acknowledge financial support for this study from the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/S001506/1). The work (at King's College, London) was also supported by the Medical Research Council (MRC) Centre grant (MR/N026063/1). TB is in receipt of a PhD studentship funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. ST's lab is partly funded by MRC research grants MR/N030087/1 and MR/S00484X/1. RM is in receipt of the MRC-Sackler PhD Programme studentship as part of the MRC Centre for Neurodevelopmental Disorders (Medical Research Council MR/P502108/1). Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

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.

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