| Abstract No.: | A-C1096 |
| Country: | Canada |
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| Title: | PRENATAL IMMUNE CHALLENGE AFFECTS DEVELOPMENTAL CHANGES IN THE MORPHOLOGY OF PYRAMIDAL NEURONS OF THE PREFRONTAL CORTEX AND HIPPOCAMPUS IN RATS |
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| Authors/Affiliations: | 2 Moogeh Baharnoori*; 1 Wayne Brake; 2 Lalit.K Srivastava;
1 Centre for Studies in Behavioral Neuroscience, Concordia University , Montreal, QC, Canada; 2 Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada
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| Content: | Objectives: Maternal infection during pregnancy is known to be a risk factor for the development of schizophrenia in the offspring. Animal studies have shown that maternal administration of infectious agents and immune activators at various times of pregnancy causes long-lasting behavioral changes in the offspring that are relevant to schizophrenia, including hyperresponsiveness to stress and psychostimulants, and deficits in sensorimotor gating, social interaction and cognition. However, the neural bases of behavioral alterations in prenatal immune-challenged offspring are poorly understood. As schizophrenia is widely considered as a disorder of aberrant cortical neural development and connectivity, we hypothesized that immune activation during pregnancy may result in abnormal morphological development of neurons in the medial prefrontal cortex (mPFC) and the hippocampus. Using offspring of pregnant rat dams administered with lipopolysaccharide (LPS), a bacterial endotoxin that elicits cytokine and fever response, we investigated neonatal, pre- and post-pubertal patterns of dendritic arborization and density and structure of dendritic spines of the pyramidal neurons of the medial prefrontal cortex (mPFC) and hippocampus.
Materials and Methods: Pregnant Sprague-Dawley rats were administered with 100μg/kg of LPS twice at E15 and E16. Male pups from the dams which showed fever response to LPS were sacrificed at postnatal days (PD) 10, 35 and 60 and their brain sections were processed for modified Golgi-Cox staining. Dendritic length, branching, spine density and structure were assessed in pyramidal neurons of layer III and V of the mPFC and CA1 region of the hippocampus using Neurolucida software.
Results: At all ages, dendritic arborization 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). In CA1, LPS treatment significantly diminished spine length, volume and surface area; however the spine density was not altered. While the spine density was not altered at any age in layer III mPFC or hippocampus, it was significantly lower in the deeper layer (V) mPFC in adult LPS animals.
Conclusion: The present study provides the first evidence that prenatal exposure to LPS in rats significantly affects spatio-temporal development of the morphology of pyramidal neurons in the mPFC and hippocampus. Pyramidal neurons are the main source of excitatory glutamate neurotransmission in the central nervous system. Alterations in the structure of mPFC and hippocampal neurons may affect their ability to build appropriate connections through incoming afferents during critical stages of brain development. This may have negative impact on neuronal connectivity and functions of these structures.
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