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Postnatal Ethanol Exposure Simplifies the Dendritic Morphology of Medium Spiny Neurons Independently of Adenylyl Cyclase 1 and 8 Activity in Mice
Author(s) -
Susick Laura L.,
Lowing Jennifer L.,
Provenzano Anthony M.,
Hildebrandt Clara C.,
Conti Alana C.
Publication year - 2014
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12383
Subject(s) - dendritic spine , medium spiny neuron , adenylyl cyclase , soma , striatum , medicine , neurotoxicity , endocrinology , biology , neurodegeneration , fetus , chemistry , neuroscience , dopamine , toxicity , stimulation , hippocampal formation , pregnancy , genetics , disease
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 ( AC s) 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 AC 1/8 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 ( MSN s) 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 MSN s regardless of genotype without affecting spine density. In the absence of EtOH, genetic deletion of AC 1/8 reduced the dendritic complexity, number of branch points, spine density, and soma size of MSN s 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 MSN s and that this outcome is not altered by the functional status of AC 1 and AC 8. Therefore, although deletion of AC 1/8 demonstrates a role for the ACs in normal morphologic development and EtOH‐induced neurodegeneration, loss of AC 1/8 activity does not exacerbate the effects of EtOH on dendritic morphology or spine density.