title: Ethanol-Induced Neurodegeneration and Glial Activation in the Developing Brain.
abstract: Ethanol induces neurodegeneration in the developing brain, which may partially explain the long-lasting adverse effects of prenatal ethanol exposure in fetal alcohol spectrum disorders (FASD). While animal models of FASD show that ethanol-induced neurodegeneration is associated with glial activation, the relationship between glial activation and neurodegeneration has not been clarified. This review focuses on the roles of activated microglia and astrocytes in neurodegeneration triggered by ethanol in rodents during the early postnatal period (equivalent to the third trimester of human pregnancy). Previous literature indicates that acute binge-like ethanol exposure in postnatal day 7 (P7) mice induces apoptotic neurodegeneration, transient activation of microglia resulting in phagocytosis of degenerating neurons, and a prolonged increase in glial fibrillary acidic protein-positive astrocytes. In our present study, systemic administration of a moderate dose of lipopolysaccharides, which causes glial activation, attenuates ethanol-induced neurodegeneration. These studies suggest that activation of microglia and astrocytes by acute ethanol in the neonatal brain may provide neuroprotection. However, repeated or chronic ethanol can induce significant proinflammatory glial reaction and neurotoxicity. Further studies are necessary to elucidate whether acute or sustained glial activation caused by ethanol exposure in the developing brain can affect long-lasting cellular and behavioral abnormalities observed in the adult brain.
authors.affiliation: Division of Neurochemisty, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Orangeburg, NY 10962, USA. marsaito@nki.rfmh.org.|Department of Psychiatry, New York University Langone Medical Center, 550 First Avenue, New York, NY 10016, USA. marsaito@nki.rfmh.org.
authors.forename: Mariko
authors.initials: M
authors.lastname: Saito
authors.affiliation: Division of Neurochemisty, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Orangeburg, NY 10962, USA. chakrabortyg@aol.com.
authors.forename: Goutam
authors.initials: G
authors.lastname: Chakraborty
authors.affiliation: Division of Neurochemisty, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Orangeburg, NY 10962, USA. mhui@nki.rfmh.org.
authors.forename: Maria
authors.initials: M
authors.lastname: Hui
authors.affiliation: Division of Neurochemisty, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Orangeburg, NY 10962, USA. kmasiello@nki.rfmh.org.
authors.forename: Kurt
authors.initials: K
authors.lastname: Masiello
authors.affiliation: Department of Psychiatry, New York University Langone Medical Center, 550 First Avenue, New York, NY 10016, USA. mitsaito@nki.rfmh.org.|Division of Analytical Psychopharmacology, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Orangeburg, NY 10962, USA. mitsaito@nki.rfmh.org.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Saito
keywords: astrocytes; developing brain; ethanol; fetal alcohol spectrum disorders; glial activation; lipopolysaccharides; microglia; neurodegeneration; neuroinflammation; phagocytosis