Epidemiological evidence implicates maternal infection as a risk factor for autism spectrum disorder and schizophrenia. Animal models corroborate this link and demonstrate that maternal immune activation (MIA) alone is sufficient to impart lifelong neuropathology and altered behaviors in offspring. This review describes common principles revealed by these models, highlighting recent findings that strengthen their relevance for schizophrenia and autism and are starting to reveal the molecular mechanisms underlying the effects of MIA on offspring. The role of MIA as a primer for a much wider range of psychiatric and neurologic disorders is also discussed. Finally, the need for more research in this nascent field and the implications for identifying, and developing new treatments for, individuals at heightened risk for neuro-immune disorders are considered.

Increasing evidence points to a central role for immune dysregulation in autism spectrum disorder (ASD). Several ASD risk genes encode components of the immune system and many maternal immune system-related risk factors — including autoimmunity, infection and fetal reactive antibodies — are associated with ASD. In addition, there is evidence of ongoing immune dysregulation in individuals with ASD and animal models of this disorder. Recently, several molecular signalling pathways have been identified that link immune activation to ASD phenotypes, including pathways downstream of cytokines, hepatocyte growth factor receptor (MET), MHCI molecules, microglia and complement factors. These findings indicate that the immune system is a point of convergence for various ASD-related genetic and environmental risk factors.

OBJECTIVE-Emerging data demonstrate that maternal diabetes has long-term health consequences for offspring, including the development of hypertension. In adults, circulating endothelial progenitor cells (EPCs) participate in vascular repair, and EPC numbers and function inversely correlate with the risk of developing vascular disease. Therefore, our objectives were to determine whether hyperglycemia or exposure to a diabetic intrauterine environment alters EPC function. RESEARCH DESIGN AND METHODS-We used well-established clonogenic endothelial colony-forming cell (ECFC) assays and murine transplantation experiments to examine human vasculogenesis.RESULTS-Both in vitro hyperglycemia and a diabetic intrauterine environment reduced ECFC colony formation, self-renewal capacity, and capillary-like tube formation in matrigel. This cellular phenotype was linked to premature senescence and reduced proliferation. Further, cord blood ECFCs from diabetic pregnancies formed fewer chimeric vessels de novo after transplantation into immunodeficient mice compared with neonatal ECFCs harvested from uncomplicated pregnancies. CONCLUSIONS-Collectively, these data demonstrate that hyperglycemia or exposure to a diabetic intrauterine environment diminishes neonatal ECFC function both in vitro and in vivo, providing potential mechanistic insights into the long-term cardiovascular complications observed in newborns of diabetic pregnancies. Diabetes 57:724-731, 2008

Objective We sought to identify and characterize two distinct populations of bona fide circulating endothelial cells, including the endothelial colony forming cell (ECFC), by polychromatic flow cytometry (PFC), colony assays, immunomagnetic selection, and electron microscopy. Methods and Results Mononuclear cells from human umbilical cord blood and peripheral blood were analyzed utilizing our recently published PFC protocol. A population of cells containing both ECFCs and mature circulating endothelial cells (CEC) were determined by varying expressions of CD34, CD31 and CD146, but not AC133 and CD45. After immunomagnetic separation, these cells failed to form hematopoietic colonies, yet clonogenic endothelial colonies with proliferative potential were obtained, thus verifying their identity as ECFCs. The frequency of ECFCs were increased in cord blood and were extremely rare in the peripheral blood of healthy adults. In addition, we also detected another mature endothelial cell population in the circulation that was apoptotic. Finally, when comparing this new protocol to a prior method we determined that the present protocol identifies circulating endothelial cells while the earlier protocol identified extracellular vesicles. Conclusions Two populations of circulating endothelial cells including the functionally characterized ECFC are now identifiable in human cord blood and peripheral blood by PFC.