lntrauterine environment - genome interaction and Chitdren ' s development ( 2 ) : Brain structure impairment and behavioral disturbance induced in male mice offspring by a single intraperitoneal administration of domoic acid ( DA ) to their dams

To demonstrate induction of delayed central nervous toxicity by disturbing neuronal activities in the devetoping brain, we administered a single intraperitoneal dose of domoic acid CDA; 1 mgfkg), a potent glutamate receptor agonist, to pregnant female mice at the gestational day of 1 1 ,5, 14.5 or 17.5, The dams had recovered from acute symptoms within 24 hr, followed by normal delivery, feeding and weaning. All male otiSpring mice after weaning were apparently normal in response to handlers during cage maintenance, body weight measurement and to mate miee in group housing conditions. At the age of 1 1 weeks, our neurobehavior testing battery revealed severe impairment oflearning and rnemory with serious deviances of anxiety-related behaviors. The devetoped brain ofprenatally exposed mice showed myelination failure and the overgrowth of neuronal processes ofthe limbic coitex neurons. This study indicates that the temporal disturbance of neurotransmission ofthe developing brain induces irreversible structural and functional damage to Qffspring which becomes monitorable in their adulthood by a proper battery ofneurobehavioral tests.