ABSTRACT
<p><b>OBJECTIVE</b>To investigate effect of inhibiting melatonin biosynthesis on activities of protein kinase A (PKA), glycogen synthase kinase-3 (GSK-3) and tau phosphorylation at PS214 and M4 epitopes using haloperidol, a specific inhibitor of 5-hydroxyindole-O-methyltransferase.</p><p><b>METHODS</b>Brain ventricular and intraperitoneal injections were used for haloperidol administration, Western blots for tau phosphorylation, 32P-labeling for PKA and GSK-3 activity, and high performance liquid chromatograph for detection of serum melatonin levels.</p><p><b>RESULTS</b>Haloperidol injection through the lateral ventricle and intraperitoneal reinforcement significantly stimulated PKA activity with a concurrent hyperphosphorylation of tau at M4 (Thr231/Ser235) and PS214 (Ser214) sites. Prior treatment of the rats using melatonin supplement for one week and reinforcement during the haloperidol administration arrested PKA activity and attenuated tau hyperphosphorylation. GSK-3 activity showed no obvious change after haloperidol injection, however, melatonin supplements and reinforcements during haloperidol infusion inactivated basal activity of GSK-3.</p><p><b>CONCLUSION</b>Decreased melatonin may be involved in Alzheimer-like tau hyperphosphorylation, and overactivation of PKA may play a crucial role in this process.</p>
Subject(s)
Animals , Male , Rats , Cyclic AMP-Dependent Protein Kinases , Metabolism , Epitopes , Glycogen Synthase Kinase 3 , Metabolism , Haloperidol , Pharmacology , Hippocampus , Metabolism , Injections, Intraperitoneal , Injections, Intraventricular , Melatonin , Blood , Phosphorylation , Rats, Wistar , tau Proteins , MetabolismABSTRACT
The progress is reviewed on the studies of procyanicdins biological and pharmacological activities in the past ten years, including antioxidant, protecting cardiovascular system, regulating immunocompetence, antiviral, anticancer, antiulcer and antidepressant, antimutagenic properties, etc.