Diabetes-induced alteration in brain monoamine metabolism in rats

Concentrations of monoamines and their metabolites as well as the activities of tyrosine hydroxylase (TH) and of choline acetyltransferase were investigated in various brain regions of control and streptozotocin-treated Sprague-Dawley rats. The animals were rendered diabetic by a single i.v. injection of streptozotocin (65 mg/kg) and killed 10, 30 and 90 days after the treatment. During the course of diabetes, progressive decreases in the activity of TH and a marked increase in the concentration of norepinephrine were observed in several brain regions, including thalamus, hypothalamus, medulla and midbrain. This inverse relationship between TH activity and norepinephrine content was also seen in the pons but only in the 90-day diabetic animals. Lower TH activity in the hypothalamus of 30-day diabetic rats reflected a decreased Vmax, but no difference in the Km. The number of alpha adrenergic receptors was increased significantly in the hypothalamus, medulla and midbrain of the 30-day diabetic rats. The concentrations of dopamine and serotonin in various brain regions of the 10- and 30-day diabetic rats were generally not significantly different from controls. Concentrations of the acidic metabolites of these neurotransmitters, dihydroxyphenylacetic acid and 5-hydroxyindolacetic acid, were, however, greatly reduced. The activity of choline acetyltransferase, a marker of presynaptic cholinergic neuron activity, remained unaltered during the course of diabetes. These data suggest that uncontrolled diabetes is associated with a significant disturbance of brain monoamine metabolism.