Neural Systems and Plasticity Research Group, Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada.
Neuroscience. 2012 Jan 10;201:184-98. doi: 10.1016/j.neuroscience.2011.11.011. Epub 2011 Nov 11.
Infection during pregnancy (i.e., prenatal infection) increases the risk of psychiatric illnesses such as schizophrenia and autism in the adult offspring. The present experiments examined the effects of prenatal immune challenge on behavior in three paradigms relevant to these disorders: prepulse inhibition (PPI) of the acoustic startle response, locomotor responses to an unfamiliar environment and the N-methyl-d-aspartate antagonist MK-801, and three forms of recognition memory. Pregnant Long-Evans rats were exposed to the viral mimetic polyinosinic-polycytidylic acid (PolyI:C; 4 mg/kg, i.v.) on gestational day 15. Offspring were tested for PPI and locomotor activity before puberty (postnatal days (PNDs)35 and 36) and during young adulthood (PNDs 56 and 57). Four prepulse-pulse intervals (30, 50, 80, and 140 ms) were employed in the PPI test. Recognition memory testing was performed using three different spontaneous novelty recognition tests (object, object location, and object-in-place recognition) after PND 60. Regardless of sex, offspring of PolyI:C-treated dams showed disrupted PPI at 50-, 80-, and 140-ms prepulse-pulse intervals. In the prepubescent rats, we observed prepulse facilitation for the 30-ms prepulse-pulse interval trials that was selectively retained in the adult PolyI:C-treated offspring. Locomotor responses to MK-801 were significantly reduced before puberty, whereas responses to an unfamiliar environment were increased in young adulthood. Both male and female PolyI:C-treated offspring showed intact object and object location recognition memory, whereas male PolyI:C-treated offspring displayed significantly impaired object-in-place recognition memory. Females were unable to perform the object-in-place test. The present results demonstrate that prenatal immune challenge during mid/late gestation disrupts PPI and locomotor behavior. In addition, the selective impairment of object-in-place recognition memory suggests tasks that depend on prefrontal cortex may be particularly vulnerable following prenatal immune challenge.
孕期感染（即产前感染）会增加成年后代患精神疾病的风险，如精神分裂症和自闭症。本实验通过三个与这些疾病相关的范式研究了产前免疫挑战对行为的影响：听觉惊跳反应的前脉冲抑制（PPI）、对陌生环境的运动反应以及 N-甲基-D-天冬氨酸拮抗剂 MK-801，以及三种形式的识别记忆。怀孕的长耳大仓鼠在妊娠第 15 天接受病毒模拟物聚肌胞苷酸（PolyI:C；4mg/kg，iv）。幼仔在青春期前（出生后第 35 天和第 36 天）和青年期（出生后第 56 天和第 57 天）进行 PPI 和运动活动测试。在 PPI 测试中使用了四个脉冲前脉冲间隔（30、50、80 和 140ms）。在 PND60 后，通过三种不同的自发新颖性识别测试（物体、物体位置和物体位置识别）进行识别记忆测试。无论性别如何，PolyI:C 处理的母鼠的后代在 50、80 和 140ms 脉冲前脉冲间隔试验中表现出 PPI 中断。在青春期前的大鼠中，我们观察到 30ms 脉冲前脉冲间隔试验中的脉冲前易化作用，而这种作用在成年 PolyI:C 处理的后代中选择性保留。在青春期前，MK-801 对运动的反应显著降低，而在青年期，对陌生环境的反应增加。雄性和雌性 PolyI:C 处理的后代都表现出完整的物体和物体位置识别记忆，而雄性 PolyI:C 处理的后代表现出明显的物体位置识别记忆受损。雌性无法进行物体位置测试。本研究结果表明，妊娠中期/晚期的产前免疫挑战会破坏 PPI 和运动行为。此外，物体位置识别记忆的选择性损伤表明，依赖前额叶皮层的任务在产前免疫挑战后可能特别容易受到影响。
