Long-term effects of maternal immune activation on depression-like behavior in the mouse

Depression is a debilitating mental disease affecting a large population worldwide, the pathophysiological mechanisms of which remain incompletely understood. Prenatal infection and associated activation of the maternal immune system (MIA) are prominently related to an increased risk for the develop...

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Bibliographic Details
Published in:Translational psychiatry 2014-02, Vol.4 (2), p.e363-e363
Main Authors: Khan, D, Fernando, P, Cicvaric, A, Berger, A, Pollak, A, Monje, F J, Pollak, D D
Format: Article
Language:English
Subjects:
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Animals
Behavior, Animal - physiology
Behavioral Sciences
Biological Psychology
Cognition Disorders - etiology
Depression - etiology
Disease Models, Animal
Female
Hippocampus - metabolism
Hippocampus - physiopathology
Interleukin-6 - physiology
Male
Medicine
Medicine & Public Health
Mice
Mice, Inbred C57BL
Neurosciences
Original
original-article
Pharmacotherapy
Pregnancy
Prenatal Exposure Delayed Effects - immunology
Psychiatry
Receptors, Vascular Endothelial Growth Factor - metabolism
Vascular Endothelial Growth Factor A - metabolism
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Summary:Depression is a debilitating mental disease affecting a large population worldwide, the pathophysiological mechanisms of which remain incompletely understood. Prenatal infection and associated activation of the maternal immune system (MIA) are prominently related to an increased risk for the development of several psychiatric disorders including schizophrenia and autism in the offsprings. However, the role of MIA in the etiology of depression and its neurobiological basis are insufficiently investigated. Here we induced MIA in mice by challenge with polyinosinic:polycytidylic phosphate salt—a synthetic analog of double-stranded RNA, which enhances maternal levels of the cytokine interleukin-6 (IL-6)—and demonstrate a depression-like behavioral phenotype in adult offsprings. Adult offsprings additionally show deficits in cognition and hippocampal long-term potentiation (LTP) accompanied by disturbed proliferation of newborn cells in the dentate gyrus and compromised neuronal maturation and survival. The behavioral, neurogenic and functional deficiencies observed are associated with reduced hippocampal expression of vascular endothelial growth factor (VEGF)A-VEGFR2. IL-6-STAT3-dependent aberrant VEGFA-VEGFR2 signaling is proposed as neurobiological mechanism mediating the effects of MIA on the developing fetal brain and ensuing consequences in adulthood.
ISSN:2158-3188
2158-3188
DOI:10.1038/tp.2013.132