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


OBJECTIVE
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.
Lee
Li-Yen
LY
Department of Anatomy, National University of Singapore, Singapore, 119260, Singapore.
Ong
Wei-Yi
WY
Farooqui
Akhlaq A
AA
Burgunder
Jean-Marc
JM
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001522:Behavior, Animal; D001590:Benztropine / Q000494:pharmacology / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000201:enzymology* / Q000378:metabolism; D003342:Corpus Striatum / Q000201:enzymology* / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004333:Drug Administration Routes; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009928:Organ Specificity; D063065:Organophosphonates / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D054512:Phospholipases A2, Calcium-Independent / Q000037:antagonists & inhibitors*; D011753:Pyrones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior; D013788:Thalamus / Q000201:enzymology* / Q000378:metabolism
D001095:Arachidonic Acids; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D016376:Oligonucleotides, Antisense; D063065:Organophosphonates; D010726:Phosphodiesterase Inhibitors; D011753:Pyrones; C104810:methyl arachidonylfluorophosphonate; D001590:Benztropine; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D054512:Phospholipases A2, Calcium-Independent; D002118:Calcium