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

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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.

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References

  • Ackermann EJ, Conde-Frieboes K, Dennis EA (1995) Inhibition of macrophage Ca2+-independent phospholipase A2 by bromoenol lactone and trifluoromethyl ketones. J Biol Chem 270:445–450

    Article  PubMed  CAS  Google Scholar 

  • Andreassen OA, Jorgensen HA (2000) Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats. Implications for tardive dyskinesia? Prog Neurobiol 61:525–541

    Article  PubMed  CAS  Google Scholar 

  • Andreassen OA, Ferrante RJ, Aamo TO, Beal MF, Jorgensen HA (2003) Oral dyskinesias and histopathological alterations in substantia nigra after long-term haloperidol treatment of old rats. Neuroscience 122:717–725

    Article  PubMed  CAS  Google Scholar 

  • Antony P, Freysz L, Horrocks LA, Farooqui (2001) AA Effect of retinoic acid on the Ca2+- independent phospholipase A2 in nuclei of LA-N-1 neuroblastoma cells. Neurochem Res 26:83–88

    Article  PubMed  CAS  Google Scholar 

  • Balsinde J, Dennis EA (1997) Function and inhibition of intracellular calcium-independent phospholipase A2. J Biol Chem 272:16069–16072

    Article  PubMed  CAS  Google Scholar 

  • Balsinde J, Balboa MA, Dennis EA (1997) Antisense inhibition of group VI Ca2+-independent phospholipase A2 blocks phospholipid fatty acid remodeling in murine P388D1 macrophages. J Biol Chem 272:29317–29321

    Article  PubMed  CAS  Google Scholar 

  • Balsinde J, Winstead MV, Dennis EA (2002) Phospholipase A2 regulation of arachidonic acid mobilization. FEBS Lett 531:2–6

    Article  PubMed  CAS  Google Scholar 

  • Brown WJ, Chambers K, Doody A (2003) Phospholipase A2 (PLA2) enzymes in membrane trafficking: mediators of membrane shape and function. Traffic 4:214–221

    Article  PubMed  CAS  Google Scholar 

  • Burnett GB, Prange AJ Jr, Wilson IC, Jolliff LA, Creese IC, Synder SH (1980) Adverse effects of anticholinergic antiparkinsonian drugs in tardive dyskinesia. An investigation of mechanism. Neuropsychobiology 6:109–120

    Article  PubMed  CAS  Google Scholar 

  • Cousins MS, Carriero DL, Salamone JD (1997) Tremulous jaw movements induced by the acetylcholinesterase inhibitor tacrine: effects of antiparkinsonian drugs. Eur J Pharmacol 322:137–145

    Article  PubMed  CAS  Google Scholar 

  • Egan MF, Hurd Y, Ferguson J, Bachus SE, Hamid EH, Hyde TM (1996) Pharmacological and neurochemical differences between acute and tardive vacuous chewing movements induced by haloperidol. Psychopharmacology (Berl) 127:337–345

    Article  CAS  Google Scholar 

  • Ellison G, See R, Levin E, Kinney J (1987) Tremorous mouth movements in rats administered chronic neuroleptics. Psychopharmacology (Berl) 92:122–126

    Article  Google Scholar 

  • Ellison G, Johansson P, Levin E, See R, Gunne L (1988) Chronic neuroleptics alter the effects of the D1 agonist SK&F 38393 and the D2 agonist LY171555 on oral movements in rats. Psychopharmacology 96:253–257

    Article  PubMed  CAS  Google Scholar 

  • Fahn WE, Lake CR, Gerber CJ (1974) Cholinergic suppression of tardive dyskinesia. Psychopharmacology 42:135–137

    Google Scholar 

  • Farooqui AA, Horrocks LA (2007) Glycerophospholipids in the brain: Phospholipase A2 in neurological disorders. Springer, New York

    Google Scholar 

  • Farooqui AA, Antony P, Ong WY, Horrocks LA, Freysz L (2004) Retinoic acid-mediated phospholipase A2 signaling in the nucleus. Brain Res Brain Res Rev 45:179–195

    Article  PubMed  CAS  Google Scholar 

  • Fujita S, Ikegaya Y, Nishikawa M, Nishiyama N, Matsuki N (2001) Docosahexaenoic acid improves long-term potentiation attenuated by phospholipase A2 inhibitor in rat hippocampal slices. Br J Pharmacol 132:1417–1422

    Article  PubMed  CAS  Google Scholar 

  • Gattaz WF, Kollisch M, Thuren T, Virtanen JA, Kinnunen PKJ (1987) Increased plasma phospholipase-A2 activity in schizophrenic patients: reduction after neuroleptic therapy. Biol Psychiatry 22:421–426

    Article  PubMed  CAS  Google Scholar 

  • Gattaz WF, Hubner CV, Nevalainen TJ, Thuren T, Kinnunen PK (1990) Increased serum phospholipase A2 activity in schizophrenia: a replication study. Biol Psychiatry 28:495–501

    PubMed  CAS  Google Scholar 

  • Iversen SD, Howells RB, Hughes RP (1980) Behavioral consequences of long-term treatment with neuroleptic drugs. Adv Biochem Psychopharmacol 24:305–313

    PubMed  CAS  Google Scholar 

  • Jicha GA, Salamone JD (1991) Vacuous jaw movements and feeding deficits in rats with ventrolateral striatal dopamine depletion: possible relation to parkinsonian symptoms. J Neurosci 11:3822–3829

    PubMed  CAS  Google Scholar 

  • Katzenschlager R, Sampaio C, Costa J, Lees A (2003) Anticholinergics for symptomatic management of Parkinson’s disease. Cochrane Database Syst Rev 2:CD003735

    PubMed  Google Scholar 

  • Lees A (2005) Alternatives to levodopa in the initial treatment of early Parkinson’s disease. Drugs Aging 22:731–740

    Article  PubMed  CAS  Google Scholar 

  • Martel MA, Patenaude C, Menard C, Alaux S, Cummings BS, Massicotte G (2006) A novel role for calcium-independent phospholipase A2 in alpha-amino-3-hydroxy-5-methylisoxazole-propionate receptor regulation during long-term potentiation. Eur J Neurosci 23:505–513

    Article  PubMed  Google Scholar 

  • Menard C, Patenaude C, Massicotte G (2005a) Phosphorylation of AMPA receptor subunits is differentially regulated by phospholipase A2 inhibitors. Neurosci Lett 389:51–56

    Article  PubMed  CAS  Google Scholar 

  • Menard C, Valastro B, Martel MA, Chartier E, Marineau A, Baudry M, Massicotte G (2005b) AMPA receptor phosphorylation is selectively regulated by constitutive phospholipase A2 and 5-lipoxygenase activities. Hippocampus 15:370–380

    Article  PubMed  CAS  Google Scholar 

  • Mendes CT, Gattaz WF, Schaeffer EL, Forlenza OV (2005) Modulation of phospholipase A2 activity in primary cultures of rat cortical neurons. J Neural Transm 112:1297–1308

    Article  PubMed  CAS  Google Scholar 

  • Morgan NV, Westaway SK, Morton JE, Gregory A, Gissen P, Sonek S, Cangul H, Coryell J, Canham N, Nardocci N, Zorzi G, Pasha S, Rodriguez D, Desguerre I, Mubaidin A, Bertini E, Trembath RC, Simonati A, Schanen C, Johnson CA, Levinson B, Woods CG, Wilmot B, Kramer P, Gitschier J, Maher ER, Hayflick SJ (2006) PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron. Nat Genet 38:752–754

    Article  PubMed  CAS  Google Scholar 

  • Moriyama T, Urade R, Kito M (1999) Purification and characterization of diacylglycerol lipase from human platelets. J Biochem 125:1077–1085

    PubMed  CAS  Google Scholar 

  • Ong WY, Sandhya TL, Horrocks LA, Farooqui AA (1999) Distribution of cytoplasmic phospholipase A2 in normal rat brain. J Hirnforsch 39:391–400

    PubMed  Google Scholar 

  • Ong WY, Yeo JF, Ling SF, Farooqui AA (2005) Distribution of calcium-independent phospholipase A2 (iPLA2) in monkey brain. J Neurocytol 34:447–458

    Article  PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic, San Diego

    Google Scholar 

  • Ross BM, Hudson C, Erlich J, Warsh JJ, Kish SJ (1997) Increased phospholipids breakdown in schizophrenia. Evidence for the involvement of a calcium-independent phospholipase A2. Arch Gen Psychiatry 54:487–494

    PubMed  CAS  Google Scholar 

  • Ross BM, Hughes B, Kish SJ, Warsh JJ (2006) Serum calcium-independent phospholipase A2 activity in bipolar affective disorder. Bipolar Disord 8:265–270

    Article  PubMed  CAS  Google Scholar 

  • Salamone JD, Lalies MD, Channell SL, Iversen SD (1986) Behavioural and pharmacological characterization of the mouth movements induced by muscarinic agonists in the rat. Psychopharmacology (Berl) 88:467–471

    CAS  Google Scholar 

  • Salamone JD, Johnson CJ, McCullough LD, Steinpreis RE (1990) Lateral striatal cholinergic mechanisms involved in oral motor activities in the rat. Psychopharmacology (Berl) 102:529–534

    Article  CAS  Google Scholar 

  • Salamone JD, Mayorga AJ, Trevitt JT, Cousins MS, Conlan A, Nawab A (1998) Tremulous jaw movements in rats: a model of parkinsonian tremor. Prog Neurobiol 56:591–611

    Article  PubMed  CAS  Google Scholar 

  • Shirai Y, Ito M (2004) Specific differential expression of phospholipase A2 subtypes in rat cerebellum. J Neurocytol 33:297–307

    Article  PubMed  CAS  Google Scholar 

  • Steinpreis RE, Salamone JD (1993) Effects of acute haloperidol and reserpine administration on vacuous jaw movements in three different age groups of rats. Pharmacol Biochem Behav 46:405–409

    Article  PubMed  CAS  Google Scholar 

  • Steinpreis RE, Baskin P, Salamone JD (1993) Vacuous jaw movements induced by sub-chronic administration of haloperidol: interactions with scopolamine. Psychopharmacology (Berl) 111:99–105

    Article  CAS  Google Scholar 

  • St-Gelais F, Menard C, Congar P, Trudeau LE, Massicotte G (2004) Postsynaptic injection of calcium-independent phospholipase A2 inhibitors selectively increases AMPA receptor-mediated synaptic transmission. Hippocampus 14:319–325

    Article  PubMed  CAS  Google Scholar 

  • Strokin M, Sergeeva M, Reiser G (2003) Docosahexaenoic acid and arachidonic acid release in rat brain astrocytes is mediated by two separate isoforms of phospholipase A2 and is differently regulated by cyclic AMP and Ca2+. Br J Pharmacol 139:1014–1022

    Article  PubMed  CAS  Google Scholar 

  • Strokin M, Chechneva O, Reymann KG, Reiser G (2006) Neuroprotection of rat hippocampal slices exposed to oxygen-glucose deprivation by enrichment with docosahexaenoic acid and by inhibition of hydrolysis of docosahexaenoic acid-containing phospholipids by calcium independent phospholipase A2. Neuroscience 140:547–553

    Article  PubMed  CAS  Google Scholar 

  • Victor M, Ropper AH (2001) Adam and Victor’s Principles of Neurology, 7th edn. McGraw-Hill, New York, p 103

    Google Scholar 

  • Wolf MJ, Izumi Y, Zorumski CF, Gross RW (1995) Long-term potentiation requires activation of calcium-independent phospholipase A2. FEBS Lett 377:358–362

    Article  PubMed  CAS  Google Scholar 

  • Yang HC, Mosior M, Ni B, Dennis EA (1999) Regional distribution, ontogeny, purification, and characterization of the Ca2+-independent phospholipase A2 from rat brain. J Neurochem 73:128–1278

    Google Scholar 

  • Yeo JF, Ong WY, Ling SF, Farooqui AA (2004) Intracerebroventricular injection of phospholipases A2 inhibitors modulates allodynia after facial carrageenan injection in mice. Pain 112:148–155

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by a grant from the National University of Singapore (R-181-000-091-112). LYL is a research scholar at the NUS. There are no conflicts of interest.

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Authors and Affiliations

  1. Department of Anatomy, National University of Singapore, Singapore, 119260, Singapore

    Li-Yen Lee & Wei-Yi Ong

  2. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Jean-Marc Burgunder

  3. Neurobiology Research Programme, National University of Singapore, Singapore, 119260, Singapore

    Wei-Yi Ong & Jean-Marc Burgunder

  4. Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH, 43210, USA

    Akhlaq A. Farooqui

  5. Department of Neurology, University of Bern, 3006, Bern, Switzerland

    Jean-Marc Burgunder

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  1. Li-Yen Lee
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  2. Wei-Yi Ong
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Correspondence to Wei-Yi Ong.

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Lee, LY., Ong, WY., Farooqui, A.A. et al. Role of calcium-independent phospholipase A2 in cortex striatum thalamus cortex circuitry–enzyme inhibition causes vacuous chewing movements in rats. Psychopharmacology 195, 387–395 (2007). https://doi.org/10.1007/s00213-007-0912-y

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  • DOI: https://doi.org/10.1007/s00213-007-0912-y

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