Maternal immune activation in mice delays myelination and axonal development in the hippocampus of the offspring.
Epidemiological data suggest a relationship between maternal infection and a high incidence of schizophrenia in offspring. An animal model based on this hypothesis was made by injecting double-stranded RNA, polyinosinic-polycytidylic acid (poly-I:C), into early pregnant mice, and their offspring were examined for biochemical and histological abnormalities. Mouse brains were examined with special reference to oligodendrocytes, which have been implicated in several neurodevelopmental disorders. We detected a significant decrease of myelin basic protein (MBP) mRNA and protein at early postnatal periods in poly-I:C mice. MBP immunocytochemistry and electron microscopy revealed that the hippocampus of juvenile poly-I:C mice was less myelinated than in PBS mice, with no significant loss of oligodendrocytes. In addition, axonal diameters were significantly smaller in juvenile poly-I:C mice than in control mice. These abnormalities reverted to normal levels when the animals reached the adult stage. These findings suggest that retarded myelination and axonal abnormalities in early postnatal stages caused by maternal immune activation could be related to schizophrenia-related behaviors in adulthood.
Makinodan
Manabu
M
Department of Psychiatry, Nara Medical University Medical School, Kashihara City, Nara, Japan. mmm@naramed-u.ac.jp
Tatsumi
Kouko
K
Manabe
Takayuki
T
Yamauchi
Takahira
T
Makinodan
Eri
E
Matsuyoshi
Hiroko
H
Shimoda
Shigero
S
Noriyama
Yoshinobu
Y
Kishimoto
Toshifumi
T
Wanaka
Akio
A
D000818:Animals; D001369:Axons / Q000473:pathology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000196:embryology / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D007369:Interferon Inducers / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D004676:Myelin Basic Protein / Q000096:biosynthesis; D009186:Myelin Sheath / Q000473:pathology*; D009836:Oligodendroglia / Q000473:pathology; D010766:Phosphorylation; D011070:Poly I-C / Q000276:immunology / Q000633:toxicity; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000209:etiology
D007369:Interferon Inducers; D004676:Myelin Basic Protein; D051057:Proto-Oncogene Proteins c-akt; D011070:Poly I-C