title: Role of constitutive calcium-independent phospholipase A2 beta in hippocampo-prefrontal cortical long term potentiation and spatial working memory.
abstract: Calcium independent phospholipase A2 (iPLA2) is an 85 kDa protein that catalyzes the hydrolysis of the sn-2 acyl ester bond of glycerophospholipids to liberate free fatty acids and lysophospholipids. In this study, we determined the role of constitutive iPLA2β in long term potentiation (LTP) of the hippocampo-prefrontal cortical pathway in vivo. We also examined the effect of iPLA2β knockdown using the rewarded alternation in T-maze task, a test of spatial working memory which is dependent on this pathway. Intracortical injection of an inhibitor to iPLA2, bromoenol lactone (BEL) or antisense oligonucleotide to iPLA2β in the prefrontal cortex abolished induction of hippocampo-prefrontal cortical LTP. Moreover, iPLA2 inhibition and antisense knockdown resulted in increased errors in the rewarded alternation in T-maze task, indicating negative effects on spatial working memory. BEL or antisense injection did not produce DNA fragmentation in the cortex as demonstrated by TUNEL assay. Results confirm a role of constitutive iPLA2β in hippocampo-prefrontal cortical synaptic plasticity in vivo, and add to previous observations of a role of iPLA2 in hippocampal LTP in vitro, and long-term memory retrieval. They may be relevant in Alzheimer's disease, and other neurodegenerative conditions that are associated with changes in iPLA2.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore; Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Suku-Maran
authors.initials: SM
authors.lastname: Shalini
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore; Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Wee-Siong
authors.initials: WS
authors.lastname: Chew
authors.affiliation: Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.
authors.forename: Ramamoorthy
authors.initials: R
authors.lastname: Rajkumar
authors.affiliation: Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.
authors.forename: Gavin S
authors.initials: GS
authors.lastname: Dawe
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore; Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore. Electronic address: wei_yi_ong@nuhs.edu.sg.
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Ong
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D054512:Phospholipases A2, Calcium-Independent / Q000502:physiology*; D017397:Prefrontal Cortex / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013037:Spatial Behavior / Q000502:physiology*
chemical_list: D054512:Phospholipases A2, Calcium-Independent
keywords: Calcium independent phospholipase A2; Learning and memory; Long term potentiation; Phospholipase A2; Spatial working memory; Synaptic plasticity