Intermittent L-DOPA treatment differentially alters synaptotagmin 4 and 7 gene expression in the striatum of hemiparkinsonian rats.
Long-term use of L-DOPA in Parkinson's disease (PD) is frequently associated with side effects that are reflected in changed neurotransmitter/neuropeptide secretion in basal ganglia. These side effects could be connected with synaptotagmins (syts) because syts are involved in regulation of membrane trafficking. We have previously reported that acute L-DOPA treatment upregulated the expression of Syt 4 and Syt 7 mRNAs in hypersensitive striatum of 6-OHDA rat model for PD. Here we investigate whether intermittent L-DOPA treatment that produces behavior sensitization affects the Syt 1, Syt 2, Syt 4, Syt 7 and Syt 10 mRNAs in striatum of 6-OHDA rats killed 4 and 12 h after the last L-DOPA injection. We verified behavioral sensitization by increased intensity of contralateral turning. 6-OHDA lesion caused Syt 2 mRNA downregulation and Syt 10 mRNA upregulation in striatum, but failed to alter Syt 4, Syt 7 and Syt 1 mRNAs. Acute l-DOPA induced an increase of Syt 4 and Syt 7 mRNAs in the denervated striatum leaving the levels of Syt 1, Syt 2 and Syt 10 mRNAs unaffected. Intermittent L-DOPA treatment did not alter Syt 1, Syt 2 and Syt 10 mRNA striatal levels, suggesting that 6-OHDA-induced Syt 2 and Syt 10 mRNA changes reflect a persistent striatal abnormality caused by dopamine depletion. On contrary, intermittent L-DOPA treatment downregulated Syt 4 mRNA and prolonged the elevation of Syt 7 mRNA in the denervated striatum. We conclude that Syt 4 and Syt 7 might be specifically involved in striatal plasticity caused by repeated L-DOPA administration that accompanies sensitization.
Glavan
Gordana
G
Brain Research Laboratory, Institute for Pathophysiology, Medical Faculty, University of Ljubljana, Zaloska 4, 1000 Ljubljana, Slovenia. gordana.glavan@mf.uni-lj.si
D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D007839:Functional Laterality; D015870:Gene Expression / Q000187:drug effects*; D007980:Levodopa / Q000494:pharmacology* / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050857:Synaptotagmins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D000978:Antiparkinson Agents; D012333:RNA, Messenger; C494294:Syt4 protein, rat; C494304:Syt7 protein, rat; D050857:Synaptotagmins; D007980:Levodopa; D016627:Oxidopamine; D001058:Apomorphine