Maternal viral infection during pregnancy impairs development of fetal serotonergic neurons.
BACKGROUND
Maternal viral infection during pregnancy induces morphological abnormalities in the fetus and may cause emotional and psychological problems in offspring through unknown mechanisms. We have previously shown that prenatal exposure of rats to chemicals such as thalidomide causes an autistic-like phenotype in offspring, indicating that prenatal events affecting serotonergic development may cause developmental disorder.


METHODS
We investigated whether prenatal viral infection altered the expression of neurotransmitters involved in the emotional or psychological status of offspring. We here took advantage of the polyriboinosinic:polyribocytidylic acid (poly I:C) system, the synthetic double-stranded RNA, which is often used in animal models of viral infection.


RESULTS
Ten mg/kg of poly I:C was intraperitoneally injected on gestational day (GD) 9 and counted the numbers of serotonin-immunopositive cells on GD15 using flat whole-mount preparation method, resulting 11.1% of increase in the number of serotonergic neurons in poly I:C group. Furthermore, there was a significant decrease in hippocampal serotonin content in offspring by postnatal day 50 following poly I:C administration by high-performance liquid chromatography.


CONCLUSIONS
Since serotonin is known to link with behavior and emotion after birth, these results suggest that maternal viral infection might cause, in addition to morphological abnormalities, serotonin-related pathogenesis such as neurodevelopmental disorders including autism spectrum disorders.
Department of Developmental and Regenerative Medicine, Mie University, Graduate School of Medicine, Mie, Japan. Electronic address: tohkawara@doc.medic.mie-u.ac.jp.
Takeshi
T
Ohkawara
Department of Developmental and Regenerative Medicine, Mie University, Graduate School of Medicine, Mie, Japan.
Takashi
T
Katsuyama
Department of Developmental and Regenerative Medicine, Mie University, Graduate School of Medicine, Mie, Japan.
Michiru
M
Ida-Eto
Department of Education, Bunkyo University, Saitama, Japan.
Naoko
N
Narita
Department of Developmental and Regenerative Medicine, Mie University, Graduate School of Medicine, Mie, Japan.
Masaaki
M
Narita
D000818:Animals; D001921:Brain / Q000473:pathology*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus; D017403:In Situ Hybridization; D011070:Poly I-C / Q000633:toxicity; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000473:pathology*; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059326:Serotonergic Neurons / Q000473:pathology*; D014777:Virus Diseases / Q000150:complications*
D011070:Poly I-C
Autism; Maternal viral infection; Poly I:C; Serotonin