The purpose of this research is to determine if undernutrition during the neonatal period, at a time several regions of the CNS of mammals (rats) are still going through growth and proliferation, can render experimental subjects more vulnerable to neurotoxic insults later in life. In order to control for environmental factors (e.g. changes in maternal behavior) which inevitably confound nutritional manipulations in neonates, initial research will determine equivalent levels of malnutrition induced by three different procedures: fostering pups to non-lactating dams on several days during the first week of life, varying the number of mammae, or varying the number of pups/litter. Populations as nearly identical as possible with regard to growth curves, brain weights and standard neurochemical parameters (brain DNA, RNA and protein) will than be compared in a test of learning and memory, using a discrete trials, appetitively motivated autoshaping procedure. Other procedures used to assay neurobehavioral functioning will include kindling of convulsions by repeated immersion in heated water, and pituitary adrenal response to stress. Finally, apparently normal rats, malnourished by three procedures as neonates, will be treated with neurotoxins as adults, to determine, using neurobehavioral tests, if they are differentially vulnerable to neurotoxic insult. Toxicants to be used include p-bromephenylacetyl-urea (BPAU) which primarily affects the peripheral nervous system, methyl mecury, a substance which has peupheral effects similar to those produced by BPAU, but which also damages the central nervous system (CNS), and trimethyltin, a substance which primarily affects CNS limbic structures.

Project Start
1985-09-01
Project End
1989-03-31
Budget Start
1987-09-01
Budget End
1989-03-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Sparber, S B; O'Callaghan, J P; Berra, B (1992) Ganglioside treatment partially counteracts neurotoxic effects of trimethyltin but may itself cause neurotoxicity in rats: experimental results and a critical review. Neurotoxicology 13:679-700
Cohen, C A; Tonkiss, J; Sparber, S B (1991) Acute opiate withdrawal in rats undernourished during infancy: impact of the undernutrition method. Pharmacol Biochem Behav 39:329-35
Messing, R B; Bollweg, G; Chen, Q et al. (1988) Dose-specific effects of trimethyltin poisoning on learning and hippocampal corticosterone binding. Neurotoxicology 9:491-502
Gerbec, E N; Messing, R B; Sparber, S B (1988) Parallel changes in operant behavioral adaptation and hippocampal corticosterone binding in rats treated with trimethyltin. Brain Res 460:346-51
Sparber, S B; Cohen, C A; Messing, R B (1988) Reversal of a trimethyltin-induced learning deficit by desglycinamide-8-arginine vasopressin. Life Sci 42:171-7
Tonkiss, J; Cohen, C A; Sparber, S B (1988) Different methods for producing neonatal undernutrition in rats cause different brain changes in the face of equivalent somatic growth parameters. Dev Neurosci 10:141-51
Huang, M S; Messing, R B; Sparber, S B (1987) Learning enhancement and behavioral arousal induced by yohimbine. Life Sci 41:1083-8
Cohen, C A; Messing, R B; Sparber, S B (1987) Selective learning impairment of delayed reinforcement autoshaped behavior caused by low doses of trimethyltin. Psychopharmacology (Berl) 93:301-7
Messing, R B; Sparber, S B (1986) Increased forebrain beta-adrenergic ligand binding induced by trimethyltin. Toxicol Lett 32:107-12
Sparber, S B (1986) Developmental effects of narcotics. Neurotoxicology 7:335-48