title: Lithium protects against glucocorticoid induced neural progenitor cell apoptosis in the developing cerebellum.
abstract: Respiratory dysfunction is one of the most common causes of death associated with premature birth (Barton et al., 1999). In the United States, 7-10% of pregnant women receive antenatal glucocorticoid (GC) therapy (Matthews et al., 2004), while approximately 19% of very low birth weight infants receive postnatal GC therapy (Jobe, 2009). Clinical research suggests that GC treatment causes permanent neuromotor and cognitive deficits (Yeh et al., 2004) and stunts cerebellar growth (Parikh et al., 2007; Tam et al., 2011). We previously reported that GC-mediated neural progenitor cell (NPC) apoptosis may be responsible for cerebellar neuropathology (Maloney et al., 2011; Noguchi et al., 2008, 2011). The goal of the current study was to determine whether lithium protects NPCs from GC neuroapoptosis in vivo and in vitro. Given that it protects against a range of brain insults, we hypothesized that lithium would significantly attenuate GC induced NPC toxicity. We report that acute lithium pretreatment provides potent, cell-intrinsic neuroprotection against GC induced NPC toxicity in vivo and in vitro.
authors.affiliation: Washington University in Saint Louis, School of Medicine, Department of Genetics, Saint Louis, MO 63110, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Cabrera
authors.affiliation: Washington University in Saint Louis, School of Medicine, Department of Genetics, Saint Louis, MO 63110, USA; Washington University in Saint Louis, School of Medicine, Department of Psychiatry, Saint Louis, MO 63110, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Dougherty
authors.affiliation: Washington University in Saint Louis, School of Medicine, Department of Genetics, Saint Louis, MO 63110, USA; Washington University in Saint Louis, School of Medicine, Department of Psychiatry, Saint Louis, MO 63110, USA.
authors.forename: Sukrit
authors.initials: S
authors.lastname: Singh
authors.affiliation: Washington University in Saint Louis, School of Medicine, Department of Genetics, Saint Louis, MO 63110, USA.
authors.forename: Brant S
authors.initials: BS
authors.lastname: Swiney
authors.affiliation: Washington University in Saint Louis, School of Medicine, Department of Genetics, Saint Louis, MO 63110, USA.
authors.forename: Nuri B
authors.initials: NB
authors.lastname: Farber
authors.affiliation: Washington University in Saint Louis, School of Medicine, Department of Genetics, Saint Louis, MO 63110, USA. Electronic address: noguchik@psychiatry.wustl.edu.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Noguchi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000254:growth & development; D003907:Dexamethasone / Q000633:toxicity*; D005938:Glucocorticoids / Q000633:toxicity*; D016651:Lithium Carbonate / Q000627:therapeutic use*; D018021:Lithium Chloride / Q000627:therapeutic use*; D051379:Mice; D058953:Neural Stem Cells / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000627:therapeutic use*
chemical_list: D005938:Glucocorticoids; D018696:Neuroprotective Agents; D016651:Lithium Carbonate; D003907:Dexamethasone; D018021:Lithium Chloride
keywords: Apoptosis; Cerebellum; Dexamethasone; External granule layer; Glucocorticoid; Lithium; Neural progenitor cell; Neuroprotection