Background
Gestational alcohol exposure causes lifelong physical and neurocognitive
deficits collectively referred to as fetal alcohol spectrum disorders (FASDs).
Micronutrient deficiencies are common in pregnancies of alcohol-abusing women. Here we
show the most common micronutrient deficiency of pregnancy, iron deficiency without
anemia, significantly worsens neurocognitive outcomes following perinatal alcohol
exposure.
Methods
Pregnant rats were fed iron-deficient (ID) or iron-sufficient diets from
gestational day 13 to postnatal day (PD) 7. Pups received alcohol (0, 3.5, 5.0 g/kg)
from PD 4–9, targeting the brain growth spurt. At PD 32, learning was assessed
using delay or trace eyeblink classical conditioning (ECC). Cerebellar interpositus
nucleus (IPN) and hippocampal CA1 cellularity was quantified using unbiased
stereology.
Results
Global ANOVA revealed that ID and alcohol separately and significantly reduced
ECC learning with respect to amplitude (p’s ≤0.001) and
CR percentage (p’s ≤0.001). Iron and alcohol interacted
to reduce CR percentage in the trace ECC task (p = 0.013). Both
ID and alcohol significantly reduced IPN (p’s <0.001) and
CA1 cellularity (p’s < 0.005). CR amplitude correlated with
IPN cellularity (Delay 0.871, Trace 0.703, p’s <0.001) and
CA1 cellularity (Delay 0.792, Trace 0.846, p’s <0.001)
across both tasks. The learning impairments persisted even through the
offsprings’ iron status had normalized.
Conclusion
Supporting our previous work, gestational ID exacerbates the associative
learning deficits in this rat model of FASD. This is strongly associated with cellular
reductions within the ECC neurocircuitry. Significant learning impairments in FASD could
be the consequence, in part, of pregnancies in which the mother was also
iron-inadequate.