NEURAL GRAFTING AS A TOOL FOR THE STUDY AND REVERSAL OF NEUROBEHAVIORAL BIRTH-DEFECTS

The transplantation of fetal neurons has gained notoriety in recent ye ars for its perceived potential to reverse neurological deficits cause d by loss of one or another neuronal population. The present paper des cribes a neural grafting approach employed by our laboratory to gain m ore insight into the drug-induced neurobehavioral teratogenicity; Mice were exposed prenatally to phenobarbital by feeding the barbiturate t o the pregnant dam on gestation days 9-18. Heroin exposure was accompl ished by injecting dams during the same gestational period. At maturit y, the drug-exposed offspring displayed profound deficits in specific behavioral tasks, suggesting alterations in the septohippocampal choli nergic pathway. Biochemically, we observed increased presynaptic activ ity in the pathway, which was not accompanied by a corresponding reduc tion in postsynaptic activity. Rather, there was a general hyperactiva tion along the different postsynaptic phases. In contrast, we noted a desensitization of protein kinase C activity in response to the exposu re of a cholinergic agonist to the drug-exposed offspring. Subsequent transplantation of embryonic cholinergic cells from normal mice to the impaired hippocampus reversed the behavioral deficits, whereas sham-o perated controls exhibited no improvement. Concomitantly, all the bioc hemical alterations studied, both presynaptic and postsynaptic, were e ither partially or completely reversed following grafting. Copyright ( C) 1996 Elsevier Science Inc.