Intrauterine environment-genome interaction and children'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 developing brain, we administered a single intraperitoneal dose of domoic acid (DA; 1 mg/kg), a potent glutamate receptor agonist, to pregnant female mice at the gestational day of 11.5, 14.5 or 17.5. The dams had recovered from acute symptoms within 24 hr, followed by normal delivery, feeding and weaning. All male offspring mice after weaning were apparently normal in response to handlers during cage maintenance, body weight measurement and to mate mice in group housing conditions. At the age of 11 weeks, our neurobehavior testing battery revealed severe impairment of learning and memory with serious deviances of anxiety-related behaviors. The developed brain of prenatally exposed mice showed myelination failure and the overgrowth of neuronal processes of the limbic cortex neurons. This study indicates that the temporal disturbance of neurotransmission of the developing brain induces irreversible structural and functional damage to offspring which becomes monitorable in their adulthood by a proper battery of neurobehavioral tests.
Tanemura
Kentaro
K
Division of Cellular & Molecular Toxicology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan.
Igarashi
Katsuhide
K
Matsugami
Toshiko-R
TR
Aisaki
Ken-ichi
K
Kitajima
Satoshi
S
Kanno
Jun
J
D000818:Animals; D001008:Anxiety Disorders / Q000139:chemically induced; D001921:Brain / Q000187:drug effects* / Q000196:embryology* / Q000473:pathology; D001925:Brain Damage, Chronic / Q000139:chemically induced* / Q000473:pathology; D003711:Demyelinating Diseases / Q000139:chemically induced; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D007859:Learning Disabilities / Q000139:chemically induced*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D009435:Synaptic Transmission / Q000187:drug effects
D018690:Excitatory Amino Acid Agonists; C012301:domoic acid; D007608:Kainic Acid