| Research Abstract |
In the animal model of dyskinesia, molecular, chemical and pharmacological studies were conducted before and after modification of dyskinetic symptoms. Results were :
(1) In the iminodipropionitrile (IDPN) -induced dyskinesia model, dopamine turnover, dopamine D1-receptor (R), D2-R,D1-R mRNA and D2-R mRNA were reduced.Chronic administration of ceruletide normalized these biochemical changes. Immunosuppressant cyclosporine A (CsA) accelerated IDPN-induced dyskinesia in behavioraly and biochemicaly.
(2) In electrophoretic mobility shift assay, CsA increased cAMP response element (CRE) binding activity in the various brain regions compared with that in the IDPN treatment alone.
(3) From the results of neuropeptide levels of IDPN-treated rat brain, neuropeptides in the basal ganglia, hindbrain and cerebral cortex may play important roles in the manifestation of dyskinetic symptoms.
(4) Striatal c-fos mRNA expression was under the control of muscarinic cholinergic receptor mechanis.
(5) In vitro cultured neuronal cells, both DNA-binding activities of AP-1 and CREB markedly decreased with 6-OHDA and H_2O_2.While in the cultured glial cells, the AP-1 binding activity was increased with 6-OHDA and H_2O_2. In vivo study, persistent increase of DNA-binding activity of AP-1 was observed in the striatum of 6-OHDA icv-injected mice even 1 week after injection.Administration of immunosuppressant FK506 corrected this increased AP-1 activity to the control levels.
Thus, immune response might be involved in pathogenesis and pathophysiology of dyskinesia through modulation of transcription factors of genes.
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