title: Postnatal ethanol exposure simplifies the dendritic morphology of medium spiny neurons independently of adenylyl cyclase 1 and 8 activity in mice.
abstract: BACKGROUND
  Fetal exposure to alcohol can have multiple deleterious effects, including learning disorders and behavioral and executive functioning abnormalities, collectively termed fetal alcohol spectrum disorders. Neonatal mice lacking both calcium-/calmodulin-stimulated adenylyl cyclases (ACs) 1 and 8 demonstrate increased vulnerability to ethanol (EtOH)-induced neurotoxicity in the striatum compared with wild-type (WT) controls. However, the developmental impact on surviving neurons is still unclear.
  
  
  METHODS
  WT and AC1/8 double knockout (DKO) mice were administered 1 dose of EtOH (2.5 g/kg) between postnatal days 5 to 7 (P5-7). At P30, brains were removed and processed for Golgi-Cox staining. Medium spiny neurons (MSNs) from the caudate putamen were analyzed for changes in dendritic complexity; number of branches, branch points and terminals, total and average dendritic length; spine density and soma size.
  
  
  RESULTS
  EtOH significantly reduced the dendritic complexity and soma size in surviving MSNs regardless of genotype without affecting spine density. In the absence of EtOH, genetic deletion of AC1/8 reduced the dendritic complexity, number of branch points, spine density, and soma size of MSNs compared with WT controls.
  
  
  CONCLUSIONS
  These data indicate that neonatal exposure to a single dose of EtOH is sufficient to cause long-term alterations in the dendritic complexity of MSNs and that this outcome is not altered by the functional status of AC1 and AC8. Therefore, although deletion of AC1/8 demonstrates a role for the ACs in normal morphologic development and EtOH-induced neurodegeneration, loss of AC1/8 activity does not exacerbate the effects of EtOH on dendritic morphology or spine density.
authors.affiliation: John D. Dingell VA Medical Center, Detroit, Michigan; Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Susick
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Lowing
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Provenzano
authors.forename: Clara C
authors.initials: CC
authors.lastname: Hildebrandt
authors.forename: Alana C
authors.initials: AC
authors.lastname: Conti
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D003712:Dendrites / Q000187:drug effects* / Q000648:ultrastructure; D000431:Ethanol / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D000431:Ethanol; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1; C118292:adenylyl cyclase 8
keywords: Caudate Putamen; Dendritic Morphology; Fetal Alcohol Syndrome