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Phospholipase D1 Ablation Disrupts Mouse Longitudinal Hippocampal Axis Organization and Functioning
Luísa Santa-Marinha1, Isabel Castanho1, Rita Ribeiro Silva1
1Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Cell Reports
|March 27, 2020
Summary
Phospholipase D1 (PLD1) generates phosphatidic acid (PA) in the hippocampus. PLD1 knockout mice exhibit altered dorsal hippocampus function, impacting memory and social behaviors.
Area of Science:
- Neuroscience
- Lipid signaling
- Molecular biology
Background:
- Phosphatidic acid (PA) is a key signaling lipid regulating synaptic plasticity.
- A longitudinal gradient of PA exists in the hippocampus, suggesting regional specialization.
Purpose of the Study:
- To investigate the role of phospholipase D1 (PLD1) in hippocampal PA production.
- To determine if PLD1-mediated PA signaling differentially affects the dorsal hippocampus (DH) and ventral hippocampus (VH).
Main Methods:
- Utilized Pld1 knockout (KO) mice.
- Performed lipidomic analysis of hippocampal tissue.
- Assessed behavioral deficits (novel object recognition, social interaction).
- Examined neuronal morphology and protein expression (GluN2A, SNAP-25).
Main Results:
- PLD1, not PLD2, is a primary source of hippocampal PA.
- PLD1 ablation predominantly impacted the DH lipidome.
- Pld1 KO mice displayed deficits in memory and social interaction.
- Disrupted dendritic arborization and reduced GluN2A/SNAP-25 levels were observed in the DH of Pld1 KO mice.
- Reduced long-term depression (LTD) induction in the DH.
Conclusions:
- PLD1-derived PA is crucial for hippocampal organization and function.
- PA signaling exhibits longitudinal specialization within the hippocampus, with PLD1 playing a key role in the DH.
- PLD1 deficiency leads to region-specific neurobiological and behavioral impairments.
