Maturation- and sex-sensitive depression of hippocampal excitatory transmission in a rat schizophrenia model.
Schizophrenia is associated with behavioral and brain structural abnormalities, of which the hippocampus appears to be one of the most consistent region affected. Previous studies performed on the poly I:C model of schizophrenia suggest that alterations in hippocampal synaptic transmission and plasticity take place in the offspring. However, these investigations yielded conflicting results and the neurophysiological alterations responsible for these deficits are still unclear. Here we performed for the first time a longitudinal study examining the impact of prenatal poly I:C treatment and of gender on hippocampal excitatory neurotransmission. In addition, we examined the potential preventive/curative effects of risperidone (RIS) treatment during the peri-adolescence period. Excitatory synaptic transmission was determined by stimulating Schaffer collaterals and monitoring fiber volley amplitude and slope of field-EPSP (fEPSP) in CA1 pyramidal neurons in male and female offspring hippocampal slices from postnatal days (PNDs) 18-20, 34, 70 and 90. Depression of hippocampal excitatory transmission appeared at juvenile age in male offspring of the poly I:C group, while it expressed with a delay in female, manifesting at adulthood. In addition, a reduced hippocampal size was found in both adult male and female offspring of poly I:C treated dams. Treatment with RIS at the peri-adolescence period fully restored in males but partly repaired in females these deficiencies. A maturation- and sex-dependent decrease in hippocampal excitatory transmission occurs in the offspring of poly I:C treated pregnant mothers. Pharmacological intervention with RIS during peri-adolescence can cure in a gender-sensitive fashion early occurring hippocampal synaptic deficits.
Department of Physiology & Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; Department of Psychology, Gordon Faculty of Social Sciences, Tel Aviv University, Tel Aviv 69978, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
Eti
E
Patrich
Strauss Center for Computational Neuroimaging, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Yael
Y
Piontkewitz
Department of Physiology & Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Asher
A
Peretz
Department of Psychology, Gordon Faculty of Social Sciences, Tel Aviv University, Tel Aviv 69978, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
Ina
I
Weiner
Department of Physiology & Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: battali@post.tau.ac.il.
Bernard
B
Attali
D000818:Animals; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011070:Poly I-C / Q000008:administration & dosage; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000008:administration & dosage; D012559:Schizophrenia / Q000139:chemically induced / Q000503:physiopathology*
D018967:Risperidone; D011070:Poly I-C
Antipsychotic drugs; Hippocampus; Maternal immune activation; Poly I:C; Risperidone; Schizophrenia