Phospholipase D1 Ablation Disrupts Mouse Longitudinal Hippocampal Axis Organization and Functioning.
Animals
Dendrites
/ metabolism
Gene Deletion
Hippocampus
/ enzymology
Lipidomics
Long-Term Synaptic Depression
Mice, Knockout
Open Field Test
Phosphatidic Acids
/ metabolism
Phospholipase D
/ metabolism
Receptors, N-Methyl-D-Aspartate
/ metabolism
Social Behavior
Synaptosomal-Associated Protein 25
/ metabolism
Task Performance and Analysis
PLD1
PLD2
dorsal hippocampus
lipidomics
lipids
long-term depression
longitudinal hippocampal axis
phospholipase D
social memory
ventral hippocampus
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
24 03 2020
24 03 2020
Historique:
received:
17
09
2019
revised:
29
01
2020
accepted:
27
02
2020
entrez:
27
3
2020
pubmed:
27
3
2020
medline:
10
4
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32209478
pii: S2211-1247(20)30283-7
doi: 10.1016/j.celrep.2020.02.102
pii:
doi:
Substances chimiques
Phosphatidic Acids
0
Receptors, N-Methyl-D-Aspartate
0
Synaptosomal-Associated Protein 25
0
phospholipase D2
EC 3.1.4.-
Phospholipase D
EC 3.1.4.4
phospholipase D1
EC 3.1.4.4
N-methyl D-aspartate receptor subtype 2A
VH92ICR8HX
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4197-4208.e6Subventions
Organisme : NINDS NIH HHS
ID : F31 NS073387
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
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.”