The role of pro-inflammatory factors in mediating the effects on the fetus of prenatal undernutrition: implications for schizophrenia.
Exposure to prenatal undernutrition or malnutrition increases the risk of schizophrenia, although little is known about the mechanism. Pro-inflammatory factors are critical in brain development, and are believed to play an important role in neurodevelopmental disorders associated with prenatal exposure to infection, including schizophrenia. However it is not known whether pro-inflammatory factors also mediate the effects on the fetus of prenatal malnutrition or undernutrition. In this study, we established a new prenatal undernourished rat model induced by maternal exposure to a diet restricted to 50% of the low (6%) protein diet (RLP50). We observed the disappearance of maternal nest-building behavior in the RLP50 dams, increased levels of TNFA and IL6 in the placentas (P<0.001; P=0.879, respectively) and fetal livers (P<0.001; P<0.05, respectively), and a decrease in the fetal brains (P<0.05; P<0.01, respectively). Our results are similar to previous studies of maternal infection, which implies that a common pathway mediated by pro-inflammatory factors may contribute to the brain development, consequently increasing the risk of schizophrenia and other psychiatric diseases programmed by varied maternal adversities. We also provide a new prenatal undernourished model for researching prenatal problems, which differs from previous malnourished model in terms of the maternal behavior of dams and of observed pro-inflammatory factor levels in fetal tissues.
Shen
Q
Q
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, China.
Li
Z Q
ZQ
Sun
Y
Y
Wang
T
T
Wan
C L
CL
Li
X W
XW
Zhao
X Z
XZ
Feng
G Y
GY
Li
Sh
Sh
St Clair
D
D
He
L
L
Yu
L
L
D000818:Animals; D001921:Brain / Q000276:immunology; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008099:Liver / Q000196:embryology / Q000276:immunology; D044342:Malnutrition / Q000196:embryology / Q000276:immunology*; D008425:Maternal Behavior / Q000502:physiology; D009425:Nesting Behavior / Q000502:physiology; D010920:Placenta / Q000196:embryology / Q000276:immunology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011502:Protein-Energy Malnutrition / Q000196:embryology / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha