Postnatal Ethanol Exposure Simplifies the Dendritic Morphology of Medium Spiny Neurons Independently of Adenylyl Cyclase 1 and 8 Activity in Mice

Authors

  • Laura L. Susick,

    1. John D. Dingell VA Medical Center, Detroit, Michigan
    2. Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan
    Search for more papers by this author
  • Jennifer L. Lowing,

    1. John D. Dingell VA Medical Center, Detroit, Michigan
    2. Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan
    Search for more papers by this author
  • Anthony M. Provenzano,

    1. John D. Dingell VA Medical Center, Detroit, Michigan
    2. Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan
    Search for more papers by this author
  • Clara C. Hildebrandt,

    1. John D. Dingell VA Medical Center, Detroit, Michigan
    2. Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan
    Search for more papers by this author
  • Alana C. Conti

    Corresponding author
    1. John D. Dingell VA Medical Center, Detroit, Michigan
    2. Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan
    • Reprint requests: Alana C. Conti, Department of Neurosurgery, Wayne State University, 4646 John R Street (11R), Detroit MI 48201; Tel.: 313-576-3311; Fax: 313-576-1112; E-mail: aconti@med.wayne.edu

    Search for more papers by this author

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.

Ancillary