Effects of Neonatal Infection, Perinatal Malnutrition, and Crowding on Cateci{olamine Metabolism of Brain by Chi-jen Lee and Rene Dubos

Physiological and environmental stresses have been shown to alter the catecholamine metabolism of brain. For example, electric shocks (1) and cold exposure (2) significantly reduce the brain content of norepinephrine. In mice, psychosocial stimulation leads to a marked increase in the catecholamine content and in the enzymatic activities of phenylethanolamine-N-methyl transferase (PNMT), monoamine oxidase, and tyrosine hydroxylase. In contrast, isolation decreased PNMT and tyrosine hydroxylase activities but not the concentration of catecholamines (3). Pharmacologically induced increases in nerve activity (4) and various types of stress (5, 6) all lead to an increase in the activity of enzymes involved in catecholamine synthesis. The catecholamine content of the adrenergic neuron may remain constant despite marked fluctuations in the competing processes of biosynthesis and utilization of catecholamine. Measurement of the rate of conversion of radioactive precursors into specific catecholamine, or the rate of catecholamine turnover, therefore constitutes more reliable index of catecholamine metabolism than do tissue levels. In previous publications we have described the lasting biological effects of neonatal infection and early undernutrition on the physical development and brain metabolism of specific pathogen-free mice. These stresses decrease the biosynthesis of brain protein and ribonucteic acid (7), alter cyclic adenosine 3',St-monophosphate (cyclic AMP) 1 metabolism, and impair binding ability of cyclic AMP to synaptosomes (8); the synaptosomes may play a role in catecholamine storage and release, synaptic function, and processes mediated by neurohormones (9, 10).