title: Fetal alcohol spectrum disorders and neuroimmune changes.
abstract: The behavioral consequences of fetal alcohol spectrum disorders (FASD) are serious and persist throughout life. The causative mechanisms underlying FASD are poorly understood. However, much has been learned about FASD from human structural and functional studies as well as from animal models, which have provided a greater understanding of the mechanisms underlying FASD. Using animal models of FASD, it has been recently discovered that ethanol induces neuroimmune activation in the developing brain. The resulting microglial activation, production of proinflammatory molecules, and alteration in expression of developmental genes are postulated to alter neuron survival and function and lead to long-term neuropathological and cognitive defects. It has also been discovered that microglial loss occurs, reducing microglia's ability to protect neurons and contribute to neuronal development. This is important, because emerging evidence demonstrates that microglial depletion during brain development leads to long-term neuropathological and cognitive defects. Interestingly, the behavioral consequences of microglial depletion and neuroimmune activation in the fetal brain are particularly relevant to FASD. This chapter reviews the neuropathological and behavioral abnormalities of FASD and delineates correlates in animal models. This serves as a foundation to discuss the role of the neuroimmune system in normal brain development, the consequences of microglial depletion and neuroinflammation, the evidence of ethanol induction of neuroinflammatory processes in animal models of FASD, and the development of anti-inflammatory therapies as a new strategy for prevention or treatment of FASD. Together, this knowledge provides a framework for discussion and further investigation of the role of neuroimmune processes in FASD.
authors.affiliation: Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Drew
authors.affiliation: Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. Electronic address: kanecynthiaj@uams.edu.
authors.forename: Cynthia J M
authors.initials: CJ
authors.lastname: Kane
mesh_terms: D000818:Animals; D063647:Fetal Alcohol Spectrum Disorders / Q000276:immunology* / Q000503:physiopathology*; D006801:Humans; D015213:Neuroimmunomodulation / Q000502:physiology*
keywords: Alcohol; Brain development; Chemokine; Cytokine; Fetal alcohol spectrum disorders; Microglia; Neuroimmune; Neuroinflammation; Therapeutics; Toll-like receptor