MIA preclinical murine model of neurodevelopmental disorders and mental illness.

Extensive scientific evidence suggests that neurodevelopmental disturbance in pre-natal stages plays an important role in the later development of pathologies such as autism spectrum disorders and schizophrenia. Numerous studies have suggested a link between cytokine elevation via maternal immune activation (MIA) and alterations in the fetal brain. In particular, recent studies have shown that neurogenesis is modulated by inflammatory cytokines generated in response to MIA. The present line of research aims to study the possible failure of early postnatal neurogenesis in a murine model of MIA and its consequences for early neurodevelopment. 

A prenatal infection during the first or second trimester of pregnancy can alter one’s neurodevelopment and increase the risk of psychiatric disorders such as schizophrenia. In this project we worked with a model of maternal immune activation disease (MIA), Poly (I:C). This synthetic double-stranded RNA analog binds to TLR3 recognizing pathogens and triggers the genes and proteins expression of innate immune response. Thus, it initiates a maternal immune response that increases pro-inflammatory cytokines in the placenta, amniotic fluid and fetal brain. It also activates microglia, causing neuronal apoptosis, as well as behavioral, neurochemical and structural defects. 

This line of research is aimed at: 

  1. qPCR analysis of treatment-quality neuroinflammation markers (spleen and placenta) in both mothers and controls as well as in offspring. 
  2. Phenotypic characterization of this MIA model with injection to pregnant mice on gestational day 9.5.  
  3. Histological, biochemical and cytoarchitectonic studies of brain regions involved in schizophrenia. 
  4. Translation of obtained results and applicability in clinical practice.