Intermittent L-DOPA treatment differentially alters synaptotagmin 4 and 7 gene expression in the striatum of hemiparkinsonian rats

Brain Res. 2008 Oct 21:1236:216-24. doi: 10.1016/j.brainres.2008.07.071. Epub 2008 Jul 29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antiparkinson Agents / pharmacology*
  • Antiparkinson Agents / therapeutic use
  • Apomorphine / pharmacology
  • Behavior, Animal / drug effects
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Disease Models, Animal
  • Female
  • Functional Laterality
  • Gene Expression / drug effects*
  • Levodopa / pharmacology*
  • Levodopa / therapeutic use
  • Motor Activity / drug effects
  • Oxidopamine
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / drug therapy
  • Parkinsonian Disorders / pathology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Synaptotagmins / genetics
  • Synaptotagmins / metabolism*
  • Time Factors

Substances

  • Antiparkinson Agents
  • RNA, Messenger
  • Syt4 protein, rat
  • Syt7 protein, rat
  • Synaptotagmins
  • Levodopa
  • Oxidopamine
  • Apomorphine