Increased white matter neuron density in a rat model of maternal immune activation — Implications for schizophrenia

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Abstract

Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (IWMN) density in the fibre tracts below the cortex in people with schizophrenia. The current study assesses IWMN pathology in a model of maternal immune activation (MIA); a risk factor for schizophrenia. Experimental MIA was produced by an injection of polyinosinic:polycytidylic acid (PolyI:C) into pregnant rats on gestational day (GD) 10 or GD19. A separate control group received saline injections. The density of neuronal nuclear antigen (NeuN+) and somatostatin (SST+) IWMNs was determined in the white matter of the corpus callosum in two rostrocaudally adjacent areas in the 12 week old offspring of GD10 (n = 10) or GD19 polyI:C dams (n = 18) compared to controls (n = 20). NeuN+ IWMN density trended to be higher in offspring from dams exposed to polyI:C at GD19, but not GD10. A subpopulation of these NeuN+ IWMNs was shown to express SST. PolyI:C treatment of dams induced a significant increase in the density of SST+ IWMNs in the offspring when delivered at both gestational stages with more regionally widespread effects observed at GD19. A positive correlation was observed between NeuN+ and SST+ IWMN density in animals exposed to polyI:C at GD19, but not controls. This is the first study to show that MIA increases IWMN density in adult offspring in a similar manner to that seen in the brain in schizophrenia. This suggests the MIA model will be useful in future studies aimed at probing the relationship between IWMNs and schizophrenia.

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