1. Phospholipase D1 Ablation Disrupts Mouse Longitudinal Hippocampal Axis Organization and Functioning.
- Author
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Santa-Marinha L, Castanho I, Silva RR, Bravo FV, Miranda AM, Meira T, Morais-Ribeiro R, Marques F, Xu Y, Point du Jour K, Wenk M, Chan RB, Di Paolo G, Pinto V, and Oliveira TG
- Subjects
- Animals, Dendrites metabolism, Lipidomics, Long-Term Synaptic Depression, Mice, Knockout, Open Field Test, Phosphatidic Acids metabolism, Receptors, N-Methyl-D-Aspartate metabolism, Social Behavior, Synaptosomal-Associated Protein 25 metabolism, Task Performance and Analysis, Gene Deletion, Hippocampus enzymology, Hippocampus physiology, Phospholipase D metabolism
- Abstract
Phosphatidic acid (PA) is a signaling lipid involved in the modulation of synaptic structure and functioning. Based on previous work showing a decreasing PA gradient along the longitudinal axis of the rodent hippocampus, we asked whether the dorsal hippocampus (DH) and the ventral hippocampus (VH) are differentially affected by PA modulation. Here, we show that phospholipase D1 (PLD1) is a major hippocampal PA source, compared to PLD2, and that PLD1 ablation affects predominantly the lipidome of the DH. Moreover, Pld1 knockout (KO) mice show specific deficits in novel object recognition and social interaction and disruption in the DH-VH dendritic arborization differentiation in CA1/CA3 pyramidal neurons. Also, Pld1 KO animals present reduced long-term depression (LTD) induction and reduced GluN2A and SNAP-25 protein levels in the DH. Overall, we observe that PLD1-derived PA reduction leads to differential lipid signatures along the longitudinal hippocampal axis, predominantly affecting DH organization and functioning., Competing Interests: Declaration of Interests G.D.P. is a full-time employee of Denali Therapeutics. G.D.P. and T.G.O. are listed as inventors on the patent number WO2010138869A1, “Modulation of Phospholipase D for the Treatment of Neurodegenerative Disorders.” R.B.C., G.D.P., and T.G.O. are listed as inventors on the patent number US20120302604A1, “Modulation of Phospholipase D for the Treatment of the Acute and Chronic Effects of Ethanol.”, (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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