ArticleMolecular psychiatry2018
Synaptic phospholipids as a new target for cortical hyperexcitability and E/I balance in psychiatric disorders.
Article in Molecular psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- Immune-mediated excitotoxicity in brain disorders.Nature reviews. Immunology · 2026Review
- Liver-nervous system axis: pathways, dysregulation, and translational perspectives.Journal of neuroinflammation · 2026Review
- Compromised hepatic bilirubin clearance drives depressive symptoms via regulating microglial engulfment of dendritic spines.Journal of neuroinflammation · 2026Article
- Perinatal omega-3 sex-selectively mitigates neuropsychiatric impacts of prenatal THC in the cortico-striatal-hippocampal circuit.Molecular psychiatry · 2025Article
- Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.Signal transduction and targeted therapy · 2025Review
- Lysophosphatidic acid selectively modulates excitatory transmission in hippocampal neurons.Cell & bioscience · 2025Article
- PRG-1 Relieves Neonatal Stimuli-Induced Hyperalgesia and Anxiety via Stage-Specific Synapse Remodeling.CNS neuroscience & therapeutics · 2025Article
- Neural Metabolic Networks: Key Elements of Healthy Brain Function.Journal of neurochemistry · 2025Review
- Altered cortical synaptic lipid signaling leads to intermediate phenotypes of mental disorders.Molecular psychiatry · 2024Article
- From Classical to Alternative Pathways of 2-Arachidonoylglycerol Synthesis: AlterAGs at the Crossroad of Endocannabinoid and Lysophospholipid Signaling.Molecules (Basel, Switzerland) · 2024Review
- Lysophosphatidic Acid Receptors LPAR5 and LPAR2 Inversely Control Hydroxychloroquine-Evoked Itch and Scratching in Mice.International journal of molecular sciences · 2024Article
- Plasma Lysophosphatidic Acid Concentrations in Sex Differences and Psychiatric Comorbidity in Patients with Cocaine Use Disorder.International journal of molecular sciences · 2023Article
- LPA1 receptors in the lateral habenula regulate negative affective states associated with alcohol withdrawal.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Preserving stroke penumbra by targeting lipid signalling.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Modulation of working memory duration by synaptic and astrocytic mechanisms.PLoS computational biology · 2022Article
- PRG-1 prevents neonatal stimuli-induced persistent hyperalgesia and memory dysfunction via NSF/Glu/GluR2 signaling.iScience · 2022Article
- Alteration of Glycerophospholipid Metabolism in Hippocampus of Post-stroke Depression Rats.Neurochemical research · 2022Article
- Interleukin-4 receptor signaling modulates neuronal network activity.The Journal of experimental medicine · 2022Article
- Keeping Excitation-Inhibition Ratio in Balance.International journal of molecular sciences · 2022Review
- Targeting autotaxin impacts disease advance in the SOD1-G93A mouse model of amyotrophic lateral sclerosis.Brain pathology (Zurich, Switzerland) · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
Abstract
Lysophosphatidic acid (LPA) is a synaptic phospholipid, which regulates cortical excitation/inhibition (E/I) balance and controls sensory information processing in mice and man. Altered synaptic LPA signaling was shown to be associated with psychiatric disorders. Here, we show that the LPA-synthesizing enzyme autotaxin (ATX) is expressed in the astrocytic compartment of excitatory synapses and modulates glutamatergic transmission. In astrocytes, ATX is sorted toward fine astrocytic processes and transported to excitatory but not inhibitory synapses. This ATX sorting, as well as the enzymatic activity of astrocyte-derived ATX are dynamically regulated by neuronal activity via astrocytic glutamate receptors. Pharmacological and genetic ATX inhibition both rescued schizophrenia-related hyperexcitability syndromes caused by altered bioactive lipid signaling in two genetic mouse models for psychiatric disorders. Interestingly, ATX inhibition did not affect naive animals. However, as our data suggested that pharmacological ATX inhibition is a general method to reverse cortical excitability, we applied ATX inhibition in a ketamine model of schizophrenia and rescued thereby the electrophysiological and behavioral schizophrenia-like phenotype. Our data show that astrocytic ATX is a novel modulator of glutamatergic transmission and that targeting ATX might be a versatile strategy for a novel drug therapy to treat cortical hyperexcitability in psychiatric disorders.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.