Psychopharmacology

, 195:387

Role of calcium-independent phospholipase A2 in cortex striatum thalamus cortex circuitry–enzyme inhibition causes vacuous chewing movements in rats

  • Li-Yen Lee
  • Wei-Yi Ong
  • Akhlaq A. Farooqui
  • Jean-Marc Burgunder
Original Investigation

DOI: 10.1007/s00213-007-0912-y

Cite this article as:
Lee, L., Ong, W., Farooqui, A.A. et al. Psychopharmacology (2007) 195: 387. doi:10.1007/s00213-007-0912-y

Abstract

Rationale

High levels of calcium independent phospholipase A2 (iPLA2) are present in certain regions of the brain, including the cerebral cortex, striatum, and cerebellum (Ong et al. 2005).

Objectives

The present study was carried out to elucidate a possible role of the enzyme in the motor system.

Methods

The selective iPLA2 inhibitor bromoenol lactone (BEL), the nonselective PLA2 inhibitor methyl arachidonyl fluorophosphonate (MAFP), and an antisense oligonucleotide were used to interfere with iPLA2 activity in various components of the motor system. Control animals received injections of carrier (phosphate buffered saline, PBS) at the same locations. The number of vacuous chewing movements (VCM) was counted from 1 to 14 days after injection.

Results

Rats that received BEL and high-dose MAFP injections in the striatum, thalamus, and motor cortex, but not the cerebellum, showed significant increase in VCM, compared to those injected with PBS at these locations. BEL-induced VCM were blocked by intramuscular injections of the anticholinergic drug, benztropine. Increased VCM was also observed after intrastriatal injection of antisense oligonucleotide to iPLA2. The latter caused a decrease in striatal iPLA2 levels, confirming a role of decreased enzyme activity in the appearance of VCM.

Conclusions

These results suggest an important role for iPLA2 in the cortex–striatum–thalamus–cortex circuitry. It is postulated that VCM induced by iPLA2 inhibition may be a model of human parkinsonian tremor.

Keywords

Calcium independent phospholipase A2Arachidonic acidBasal gangliaParkinson’s diseaseTremor

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Li-Yen Lee
    • 1
  • Wei-Yi Ong
    • 1
    • 3
  • Akhlaq A. Farooqui
    • 4
  • Jean-Marc Burgunder
    • 2
    • 3
    • 5
  1. 1.Department of AnatomyNational University of SingaporeSingaporeSingapore
  2. 2.Department of MedicineYong Loo Lin School of Medicine, National University of SingaporeSingaporeSingapore
  3. 3.Neurobiology Research ProgrammeNational University of SingaporeSingaporeSingapore
  4. 4.Department of Molecular and Cellular BiochemistryThe Ohio State UniversityColumbusUSA
  5. 5.Department of NeurologyUniversity of BernBernSwitzerland