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.
Strauss Center for Computational Neuroimaging, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Brain Behav Immun. 2016 Jan;51:240-251. doi: 10.1016/j.bbi.2015.08.021. Epub 2015 Aug 29.
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.
精神分裂症与行为和大脑结构异常有关，其中海马体似乎是受影响最一致的区域之一。先前在精神分裂症的 poly I:C 模型上进行的研究表明，海马体突触传递和可塑性的改变发生在后代中。然而，这些研究得出了相互矛盾的结果，导致这些缺陷的神经生理改变仍不清楚。在这里，我们首次进行了一项纵向研究，检查产前 poly I:C 处理和性别对海马兴奋性神经传递的影响。此外，我们还研究了利培酮 (RIS) 在青春期前治疗对这些缺陷的潜在预防/治疗作用。通过刺激 Schaffer 侧支并监测 CA1 锥体神经元中的纤维爆发幅度和场兴奋性突触后电位 (fEPSP) 的斜率，来确定兴奋性突触传递。在雄性和雌性后代海马切片中，从出生后第 18-20 天、34 天、70 天和 90 天，测定兴奋性突触传递。在 poly I:C 组雄性后代的青少年时期，出现了海马兴奋性传递的抑制，而在雌性后代中则延迟出现，表现为成年期。此外，还发现 poly I:C 处理的母鼠的雄性和雌性成年后代的海马体体积均减小。在青春期前用 RIS 治疗完全恢复了雄性后代的这些缺陷，但部分修复了雌性后代的这些缺陷。在 poly I:C 处理的怀孕母体的后代中，海马体兴奋性传递出现了与成熟和性别相关的减少。在青春期前用 RIS 进行药物干预可以以性别敏感的方式治愈早期发生的海马突触缺陷。
