We describe here integrated studies conducted in an animal model of br
ain malformation induced by prenatal treatment with a potent antimitot
ic agent, methylazoxymethanol acetate (MAM). When given at gestational
day 15, MAM induces a marked and dose-dependent hypoplasia of cortex
and hippocampus. The alteration of specific neurotransmitter systems i
n these brain areas reflect the specificity of the damage induced by M
AM administration at this particular stage of brain development. These
animals, when adult, show impairments in learning and memory performa
nce, without gross alterations of spontaneous behavior. The impairment
in cognitive functions is correlated with changes, both in cortex and
hippocampus, of the phosphorylation state of the neuron-specific prot
ein B-50, a substrate of Protein Kinase C, known to play a key role in
synaptic plasticity. Moreover, Long-Term Potentiation (LTP), a cellul
ar model for studying synaptic plasticity associated with learning and
memory, is impaired in the hippocampal subfields affected by MAM trea
tment. All these results - obtained with anatomical, behavioral, neuro
chemical and electrophysiological studies - point to the usefulness of
this animal model to understand the long-lasting consequences of the
interference of neurotoxic compounds with the developing CNS. (C) 1994
Intox Press, Inc.