Maternal immune activation primes deficiencies in adult hippocampal neurogenesis.
Hippocampus
Human induced pluripotent stem cells
Maternal immune activation
Neurodevelopmental disorders
Neurogenesis
Prenatal insult
Psychiatric illness
Stress
Journal
Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
03
03
2021
revised:
25
06
2021
accepted:
28
07
2021
pubmed:
6
8
2021
medline:
23
9
2021
entrez:
5
8
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34352366
pii: S0889-1591(21)00285-3
doi: 10.1016/j.bbi.2021.07.021
pmc: PMC8478664
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
410-422Subventions
Organisme : Medical Research Council
ID : MR/N026063/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N030087/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L021064/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S00484X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P502108/1
Pays : United Kingdom
Informations de copyright
Copyright © 2021. Published by Elsevier Inc.
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