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<scp>TLR</scp> 3 downregulates expression of schizophrenia gene Disc1 via <scp>MYD</scp> 88 to control neuronal morphology
- Source :
- EMBO Reports
- Publication Year :
- 2016
- Publisher :
- EMBO, 2016.
-
Abstract
- Viral infection during fetal or neonatal stages increases the risk of developing neuropsychiatric disorders such as schizophrenia and autism spectrum disorders. Although neurons express several key regulators of innate immunity, the role of neuronal innate immunity in psychiatric disorders is still unclear. Using cultured neurons and in vivo mouse brain studies, we show here that Toll‐like receptor 3 (TLR3) acts through myeloid differentiation primary response gene 88 (MYD88) to negatively control Disrupted in schizophrenia 1 ( Disc1 ) expression, resulting in impairment of neuronal development. Cytokines are not involved in TLR3‐mediated inhibition of dendrite outgrowth. Instead, TLR3 signaling suppresses expression of several psychiatric disorder‐related genes, including Disc1 . The impaired dendritic arborization caused by TLR3 activation is rescued by MYD88 deficiency or DISC1 overexpression. In addition, TLR3 activation at the neonatal stage increases dendritic spine density, but narrows spine heads at postnatal day 21 (P21), suggesting a long‐lasting effect of TLR3 activation on spinogenesis. Our study reveals a novel mechanism of TLR3 in regulation of dendritic morphology and provides an explanation for how environmental factors influence mental health.
- Subjects :
- 0301 basic medicine
Dendritic spine
viruses
Biochemistry
neural development
Mice
Morphogenesis
Molecular Biology of Disease
Receptor
innate immunity
Cells, Cultured
Mice, Knockout
Neurons
biology
hemic and immune systems
Articles
Schizophrenia
Gene Knockdown Techniques
Cytokines
Neural development
Signal Transduction
dendritic spine formation
Immunology
Nerve Tissue Proteins
chemical and pharmacologic phenomena
Article
Cell Line
03 medical and health sciences
DISC1
Genetics
medicine
Animals
Humans
neonatal infection
Molecular Biology
Gene
Innate immune system
dendritic growth
Dendrites
medicine.disease
Toll-Like Receptor 3
Disease Models, Animal
030104 developmental biology
Gene Expression Regulation
Myeloid Differentiation Factor 88
TLR3
biology.protein
Neuroscience
Biomarkers
Subjects
Details
- ISSN :
- 14693178 and 1469221X
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- EMBO reports
- Accession number :
- edsair.doi.dedup.....6ff824295c1c8fa22becc9baf4441a9d