Neonatal polyI:C treatment in mice results in schizophrenia-like behavioral and neurochemical abnormalities in adulthood.
It has been reported that viral infection in the first and second trimesters of pregnancy in humans increases the risk of subsequently developing schizophrenia. To develop a mouse model of immune activation during the early postnatal period, neonatal ICR mice were repeatedly injected with polyriboinosinic-polyribocytidilic acid (polyI:C; an inducer of strong innate immune responses) for 5 days (postnatal day 2-6) which may correspond, in terms of brain development, to the early second trimester in human. Cognitive and emotional behavior as well as the extracellular level of glutamate in the hippocampus were analyzed at the age of 10-12 weeks old. PolyI:C-treated mice showed anxiety-like behavior, impairment of object recognition memory and social behavior, and sensorimotor gating deficits, as compared to the saline-treated control group. Depolarization-evoked glutamate release in the hippocampus was impaired in polyI:C-treated mice compared to saline-treated control mice. Furthermore, to investigate the effect of neonatal immune activation on the expression levels of schizophrenia-related genes, we analyzed mRNA levels in the hippocampus 2 and 24h after polyI:C treatment. No significant differences or only transient and marginal changes were observed between polyI:C-treated and saline-treated control mice in the expression levels of schizophrenia-related genes in the hippocampus.
Ibi
Daisuke
D
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University, Graduate School of Medicine, Nagoya, Aichi, Japan.
Nagai
Taku
T
Kitahara
Yuko
Y
Mizoguchi
Hiroyuki
H
Koike
Hiroyuki
H
Shiraki
Anna
A
Takuma
Kazuhiro
K
Kamei
Hiroyuki
H
Noda
Yukihiro
Y
Nitta
Atsumi
A
Nabeshima
Toshitaka
T
Yoneda
Yukio
Y
Yamada
Kiyofumi
K
D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000188:drug therapy / Q000276:immunology; D001921:Brain / Q000187:drug effects* / Q000196:embryology* / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008568:Memory / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000276:immunology; D011119:Polynucleotides / Q000008:administration & dosage* / Q000276:immunology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology* / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D055139:Sensory Gating / Q000187:drug effects / Q000276:immunology; D012919:Social Behavior
D011119:Polynucleotides; C049667:poly(rI).poly(dC); D018698:Glutamic Acid