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Early Life Stress Inhibits Expression of a Novel Innate Immune Pathway in the Developing Hippocampus

LAN WEI ; SIMEN, Arthur ; MANE, Shrikant ; KAFFMAN, Arie

Neuropsychopharmacology (New York, N.Y.), 2012-01, Vol.37 (2), p.567-580 [Periódico revisado por pares]

Basingstoke: Nature Publishing Group

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Título:
Early Life Stress Inhibits Expression of a Novel Innate Immune Pathway in the Developing Hippocampus
Autor: LAN WEI ; SIMEN, Arthur ; MANE, Shrikant ; KAFFMAN, Arie
Assuntos: Acute-Phase Proteins - biosynthesis ; Acute-Phase Proteins - genetics ; Acute-Phase Proteins - physiology ; Adults ; Animal cognition ; Animal models ; Animals ; Animals, Newborn ; Anxiety ; Anxiety - blood ; Anxiety - genetics ; Anxiety - physiopathology ; Behavior ; Behavior, Animal - physiology ; Biological and medical sciences ; Carrier Proteins - biosynthesis ; Carrier Proteins - genetics ; Carrier Proteins - physiology ; Child abuse & neglect ; Children ; Cognitive ability ; Complications ; Corticosterone - blood ; Critical period ; Critical Period (Psychology) ; Disease Models, Animal ; Down-Regulation ; Female ; genomics ; Genomics - methods ; Hippocampus ; Hippocampus - cytology ; Hippocampus - growth & development ; Hippocampus - immunology ; Hippocampus - physiopathology ; Humans ; Immune system ; Immunity, Innate - physiology ; Laboratory animals ; Lipopolysaccharides ; Male ; Maternal Deprivation ; Medical sciences ; Membrane Glycoproteins - biosynthesis ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - physiology ; Memory ; Memory Disorders - blood ; Memory Disorders - genetics ; Memory Disorders - physiopathology ; Mental disorders ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Microglia ; Neurogenesis - genetics ; Original ; Postsynaptic density proteins ; Primates ; Proteins ; Pruning ; Psychopathology ; Risk factors ; Spine ; Stress ; Stress, Psychological - blood ; Stress, Psychological - immunology ; Stress, Psychological - physiopathology ; Stress, Psychological - psychology ; Transgenic animals
É parte de: Neuropsychopharmacology (New York, N.Y.), 2012-01, Vol.37 (2), p.567-580
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Descrição: Childhood maltreatment represents a major risk factor for the development of numerous childhood psychopathologies that in many cases linger as chronic mental illnesses in adulthood. Exposing rodents or non-human primates to early life stress increases anxiety-like behaviors and impairs cognitive function in adulthood, suggesting that animal models may provide important insights into parallel developmental processes in humans. Using an unbiased genomic screen, we found that expression of lipopolysaccharide binding protein (LBP), a member of the innate immune system, is dramatically decreased in the hippocampus of pups exposed to early life stress. LBP levels peak in the normally developing hippocampus at a period of intense synaptic pruning, during which LBP is colocalized with the synaptic marker PSD95 and is found in close proximity to processes of microglia cells. Expression of LBP declines to low levels seen in adulthood at around postnatal day 30. Importantly, 30-day-old LBP knockout (k.o.) mice show increased spine density and abnormal spine morphology, suggesting that peak levels of LBP during the second and third weeks of life are necessary for normal synaptic pruning in the hippocampus. Finally, LBP k.o. mice show impaired hippocampal-dependent memory and increased anxiety-like behaviors in a manner that resembles that seen in animals exposed to early life stress. These findings describe a novel role for LBP in normal hippocampal development and raise the possibility that at least some of the behavioral sequelae of early life stress are mediated by reduced expression of LBP during a critical period of neurodevelopment.
Editor: Basingstoke: Nature Publishing Group
Idioma: Inglês

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Early Life Stress Inhibits Expression of a Novel Innate Immune Pathway in the Developing Hippocampus

LAN WEI ; SIMEN, Arthur ; MANE, Shrikant ; KAFFMAN, Arie

Basingstoke: Nature Publishing Group

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