Regulation of expression and enzymatic activities of tyrosine and tryptophan hydroxylases in rat brain after acute electroconvulsive shock

Acute electroconvulsive shock (ECS) causes a significant increase of protei n synthesis in depressive patients and such an increase raises the possibil ity that the regulation of specific proteins and enzymatic activities in th e brain might be one of the mechanisms required for the induction of long-t erm adaptive neurochemical changes after electroconvulsive therapy. In curr ent studies, we investigated and compared simultaneously the short- and lon g-term effects of an acute ECS on the expression and enzymatic activities o f both tyrosine and tryptophan hydroxylases (TH and TpOH, respectively) in different rat brain areas. Our results demonstrated that an acute ECS produ ced: (1) a long-lasting decrease in TH and TpOH protein levels in locus cer uleus (LC), ventral tegmental area (VTA) and in TpOH protein level in the r aphe centralis (RC), maximal at 72 h, with concomitant changes in mRNA leve ls and enzymatic activities in the LC only; (2) large increase of TpOH prot ein levels in the frontal cortex (Cxf) (+145%) and increase of TH protein l evels in the hippocampus (Hip) (+207%), maximal at 72 h and 7 days which wa s not accompanied by corresponding increase of in vivo enzymatic activities . Furthermore, a second ECS increased in vivo TpOH activity in the Cxf (+19 %) while decreasing K-m value (-50%) for tetrahydrobiopterin cofactor. A st ability of the observed findings on TpOH activity in the Cxf after repeated ECS might be one of the mechanisms for the antidepressant effects of elect roconvulsive therapy. (C) 2001 Elsevier Science B.V. All rights reserved.