Baharnoori, Moogeh and Brake, Wayne G. and Srivastava, Lalit
Prenatal Immune Challenge Induces Developmental Changes in the Morphology of Pyramidal Neurons of the Prefrontal Cortex and Hippocampus in Rats.
Schizophrenia Research , 107
Official URL: http://dx.doi.org/10.1016/j.schres.2008.10.003
Background -- 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).
Methods -- Pregnant Sprague-Dawley rat dams were administered with LPS (100μg/kg, at E15 and E16) or saline. The brains of offspring were processed for Golgi-Cox staining at postnatal days (PD) 10, 35 and 56. Dendritic length, branching, spine density and structure were quantified using Neurolucida software.
Results -- 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 PD10 and 35 but returned to control values at PD60. Opposite pattern was observed in CA1 region of LPS animals (normal values at PD10 and 35, but a reduction at PD60). LPS treatment significantly altered the structure of CA1 dendritic spines at PD10. Spine density was found to be significantly lower only in layer V mPFC of PD60 LPS rats.
Conclusion -- The study provides the first evidence that prenatal exposure to an immunogen dynamically affects spatio-temporal development of mPFC and hippocampal neurons that can potentially lead to aberrant neuronal connectivity and functions of these structures.
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