[Changes in brain serotonin biosynthesis in rats with diabetes mellitus induced by streptozocin: effect of insulin treatment].
OBJECTIVE
To investigate if the changes in the activity of the tryptophan-5-hydroxylase and in brain serotonin synthesis provoked by diabetes mellitus persist or return to normal in the diabetic rats submitted to treatment with insulin.


METHODS
Diabetes induced by the administration of streptozotocin in rats and their treatment with insulin was the paradigm used. At days 7, 14 and 21 of evolution, the brain serotonergic biosynthetic activity was evaluated.


RESULTS
The diabetic rats showed a significant decrease of body weight. Also, they showed a low concentration of I-tryptophan, as well as a diminution in the activity of the key enzyme tryptophan-5-hydroxylase and its product serotonin in the cerebral cortex and brainstem. Interestingly, the activity of the enzyme was higher in the brainstem from day 14, accompanied with an elevation of the neurotransmitter. The diabetic rats submitted to treatment with insulin showed a complete physical recovery and a return to normal of plasma and brain I-tryptophan. The activity of the enzyme not only normalized but was elevated and with an increase of serotonin in the brainstem and cerebral cortex.


CONCLUSIONS
The present findings confirm that diabetes mellitus produced a chronic anabolic deficit and a decrease in some brain regions of serotonin synthesis. Also, demonstrate that the diabetic rats under specific treatment with insulin had a complete physical recovery and a return to normal of the serotonin precursor in the blood and brain. However, the activity of the limiting enzyme TrpOH case was elevated with an increase of the neurotransmitter in all regions studied. Since the diabetic animal, insulin treated, does recover metabolically, the mechanism of activation of the serotonin biosynthetic path in the brain may not be dependent on the decreased availability of its precursor the free plasma I-tryptophan. Instead, it might be due to a change in the kinetics of tryptophan-5-hydroxylase, since its activity remains significantly increased in spite of plasma and brain normalization of its substrate. Altogether these changes in the biosynthesis of an important brain neurotransmitter may be of relevance in the pathophysiology of the psychoneurological complications in diabetic patients.
Manjarrez-Gutiérrez
G
G
Laboratorio de Neuroquímica del Desarrollo, Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades, Centro Médico Nacional, Siglo XXI, Instituto Méxicano del Seguro Social. willisga@df1.telmex.net.mx
Rocío Herrera-Márquez
J R
JR
Bueno-Santoyo
S
S
González-Ramírez
M
M
Hernández
J
J
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000096:biosynthesis*; D013311:Streptozocin
D007328:Insulin; D012701:Serotonin; D013311:Streptozocin
Cambios en la biosíntesis de serotonina cerebral en ratas con diabetes mellitus inducida por estreptozotocina: efecto del tratamiento con insulina.