Baharnoori Moogeh, Brake Wayne G, Srivastava Lalit K
Douglas Mental Health University Institute, Department of Psychiatry, McGill University, 6875 LaSalle Blvd, Montreal, Canada H4H 1R3 (QC).
Schizophr Res. 2009 Jan;107(1):99-109. doi: 10.1016/j.schres.2008.10.003. Epub 2008 Nov 12.
The neural mechanisms by which maternal infections increase the risk for schizophrenia are poorly understood; however, animal models using maternal administration of immune activators suggest a role for cytokine imbalance in maternal/fetal compartments. As cytokines can potentially affect multiple aspects of neuronal development and the neuropathology of schizophrenia is believed to involve subtle temporo-limbic neurodevelopmental alterations, we investigated morphological development of the pyramidal neurons of the medial prefrontal cortex (mPFC) and hippocampus in rats that were prenatally challenged with the immune activator lipopolysaccharide (LPS). Pregnant Sprague-Dawley rats were administered with LPS (at E15- E16) or saline. The brains of offspring were processed for Golgi-Cox staining at postnatal days 10, 35 and 60. Dendritic length, branching, spine density and structure were quantified using Neurolucida software. At all ages, dendritic arbor was significantly reduced in mPFC and CA1 neurons of LPS-treated animals. Dendritic length was significantly reduced in the mPFC neurons of LPS group at P10 and 35 but returned to control values at P60. Opposite pattern was observed in CA1 region of LPS animals (normal values at P10 and 35, but a reduction at P60). LPS treatment significantly altered the structure of CA1 dendritic spines at P10. Spine density was found to be significantly lower only in layer V mPFC of P60 LPS rats. The study provides the first evidence that prenatal exposure to an immune activator dynamically affects spatio-temporal development of pyramidal neurons in mPFC and hippocampal that can potentially lead to aberrant neuronal connectivity and functions of these structures.
母体感染增加精神分裂症风险的神经机制目前仍知之甚少；然而，通过给母体注射免疫激活剂的动物模型表明，细胞因子失衡在母体/胎儿区室中发挥作用。由于细胞因子可能会影响神经元发育的多个方面，且精神分裂症的神经病理学被认为涉及颞叶边缘细微的神经发育改变，因此我们研究了产前用免疫激活剂脂多糖（LPS）攻击的大鼠内侧前额叶皮质（mPFC）和海马体锥体细胞的形态发育。将怀孕的Sprague-Dawley大鼠在胚胎期第15 - 16天注射LPS或生理盐水。在出生后第10、35和60天对后代的大脑进行高尔基-考克斯染色处理。使用Neurolucida软件对树突长度、分支、棘密度和结构进行量化。在所有年龄段，LPS处理动物的mPFC和CA1神经元的树突分支均显著减少。LPS组mPFC神经元的树突长度在出生后第10天和35天显著减少，但在出生后第60天恢复到对照值。在LPS处理动物的CA1区观察到相反的模式（出生后第10天和35天为正常值，但在出生后第60天减少）。LPS处理在出生后第10天显著改变了CA1树突棘的结构。仅在出生后第60天的LPS大鼠的V层mPFC中发现棘密度显著降低。该研究首次证明，产前暴露于免疫激活剂会动态影响mPFC和海马体中锥体细胞的时空发育，这可能导致这些结构的神经元连接和功能异常。
