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Effect of Perinatal Undernutrition on the Metabolism of Catecholamines in the Rat Brain¹

Laboratory of Neuroendocrine Regulation, Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Pregnant rats were fed adequate protein (24%) or low protein (8%) diets and the pups nursed by mothers continuing on the diets. At 24 days of age, the brain norepinephrine content in undernourished progeny was only 70%, and brain dopamine only 80%, of that in well-nourished rats. Most of the dopamine deficit was localized within the neurons of the basal ganglia. These decreases in brain apparently do not reflect decreases in the activity of the principal enzymes of catecholamine biosynthesis: No dopa was detected in the brains of malnourished animals; the brain dopamine-norepinephrine ratio was not significantly elevated; and tyrosine hydroxylase was already known to be increased in brains of undernourished rats. Tyrosine, the precursor for norepinephrine and dopamine, was concentrated in the brains of undernourished rats at the expense of the rest of the body; brain tyrosine concentrations were identical in well-nourished and undernourished rats. The initial uptake of labeled norepinephrine from the cerebrospinal fluid was used as an index of the number of catecholaminergic neurons in the brain; this number apparently remained unchanged in undernourished rats. Norepinephrine turnover was decreased in the brains of undernourished rats and the half-life for norepinephrine-³H was increased. The increased brain tyrosine hydroxylase activity, selective concentration of tyrosine within the brain, and decreased turnover of brain norepinephrine all suggest that brain catecholamines are conserved when nutrient supply limits their synthesis in developing rats.

KEY WORDS: • undernutrition • catecholamines • norepinephrine • dopamine • brain development

¹ These studies were supported in part by grants from the Barra Foundation and from the United States Public Health Service (AM-14228). Presented in part at the annual meeting of the Federation of American Socfeties for Experimental Biology, Atlantic City, N. J., 1970 and the Fourth International Congress of Endocrinology, Washington, D. C., 1972.

² Present address: Laboratory of Neuropharmacology, NIMH, St. Elizabeth's Hospital, Washington, D. C. 20032.

Manuscript received 3 January 1973.

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