Establishment and Characterization of a Gnotobiotic Mouse Model with Relevance to Infection-Mediated Neurodevelopmental Disorders

• Applicant: Dr. Daniele Mattei
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2017 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 386167685

Maternal immune activation during pregnancy has been recognized as an important etiological factor for neuropsychiatric diseases with a neurodevelopmental basis such as schizophrenia and autism. This etiological factor has been mimicked in rodents via the injection of the viral mimic PolyI:C to pregnant dams. The latter is a synthetic double-stranded RNA that elicits a viral-like immune response by binding to Toll-like receptor 3 (TLR3). It has been shown that, injection of PolyI:C to pregnant dams at e.g. gestational day 9 will result in an adult offspring showing brain anatomical, cellular and biochemical correlates of schizophrenia and autism accompanied by behavioral deficits.In recent years, an important link between the gut microbiota composition in mammals and proper brain development and maturation has been highlighted and increasingly studied. This is the field of the gut-brain axis, where the bidirectional communication between the gastroinestinal (GI) tract and the CNS is studied. It has been shown that gut dysbiosis can lead to cognitive deficits and decreased hippocampal neurogenesis. It seems that the gut microbiota is able to modulate neuropsychological traits implicated in psychiatric disorders. It is therefore of high relevance to study whether an aberrant gut-brain axis contributes to the pathophysiological mechanisms of neurodevelopmental disorders. Based on the emerging evidence suggesting an important role of the gut microbiota in normal brain development, the main aim of the proposed project is to examine whether dysbiosis of the gut microbiota induced by prenatal infection functionally contributes to the subsequent emergence of behavioral and neuronal deficits.

• DFG Programme: Research Fellowships
• International Connection: Switzerland
• Host: Professor Dr. Urs Meyer