Maternal immune activation by polyriboinosinic-polyribocytidilic acid injection produces synaptic dysfunction but not neuronal loss in the hippocampus of juvenile rat offspring.
It has been suggested that maternal immune activation increases the risk of psychiatric disorders such as schizophrenia in offspring. There are many reports about hippocampal structural pathology in schizophrenia. Antipsychotic drug administration in adolescence prevented postpubertal hippocampal structural pathology in the maternal immune activation animal model. These findings suggest the possibility that maternal immune activation induces hippocampal dysfunction in juvenile offspring. To test this hypothesis, we investigated hippocampal function in juvenile offspring of maternal immune activation model rat. A synthetic double-stranded RNA polyriboinosinic-polyribocytidilic acid (Poly I:C; 4 mg/kg/day, I.P.) was injected to pregnant rats on gestation days 15 and 17, in order to cause immune activation by stimulating Toll-like receptor 3. Hippocampal synaptic function and morphology in their juvenile offspring (postnatal days 28-31) were compared to those in vehicle-injected control offspring. Field responses were recorded in the hippocampal CA1 region by stimulating commissural/Schaffer collaterals. Pre-synaptic fiber volley amplitudes (mV) and field excitatory post-synaptic potential slopes (mV/ms) were significantly lower in treated offspring. In addition, short-term synaptic plasticity, namely, the paired-pulse facilitation ratio, was significantly higher and long-term synaptic plasticity (long-term potentiation) was significantly impaired in treated offspring. Furthermore, major pre-synaptic protein (synaptophysin) expressions were decreased, but not major post-synaptic proteins (GluR1, GluR2/3, and NR1), in hippocampal CA1 of treated offspring, whereas neuronal loss was not detected in the hippocampal CA1-CA3 regions. These results indicate that maternal immune activation leads to synaptic dysfunction without neuronal loss in the hippocampus of juvenile offspring, and this may be one of the early stages of schizophrenia pathologies.
Oh-Nishi
Arata
A
Department of Molecular Neuroimaging, Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555, Japan. oh-nishi@nirs.go.jp
Obayashi
Shigeru
S
Sugihara
Izumi
I
Minamimoto
Takafumi
T
Suhara
Tetsuya
T
D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D004249:DNA Damage / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D007107:Immune System / Q000187:drug effects / Q000276:immunology*; D008297:Male; D009473:Neuronal Plasticity / Q000276:immunology; D009474:Neurons / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D011119:Polynucleotides / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000276:immunology* / Q000473:pathology; D013569:Synapses / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D009435:Synaptic Transmission / Q000276:immunology
D011119:Polynucleotides; C049667:poly(rI).poly(dC)