ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Phospholipase D1-promoted release of tissue plasminogen activator facilitates neurite outgrowth.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 43 citations in OpenAlex.
- Phospholipase D1 Attenuation Therapeutics Promotes Resilience against Synaptotoxicity in 12-Month-Old 3xTg-AD Mouse Model of Progressive Neurodegeneration.International journal of molecular sciences · 2023Article
- Microglial contributions to aberrant neurogenesis and pathophysiology of epilepsy.Neuroimmunology and neuroinflammation · 2020Article
- DDHD1, but Not DDHD2, Suppresses Neurite Outgrowth in SH-SY5Y and PC12 Cells by Regulating Protein Transport From Recycling Endosomes.Frontiers in cell and developmental biology · 2020Article
- Role of t-PA and PAI-1 variants in temporal lobe epilepsy in Chinese Han population.BMC neurology · 2019Article
- Temporal analysis of hippocampal CA3 gene coexpression networks in a rat model of febrile seizures.Disease models & mechanisms · 2018Article
- PLD1 promotes dendritic spine development by inhibiting ADAM10-mediated N-cadherin cleavage.Scientific reports · 2017Article
- Astrocyte-derived phosphatidic acid promotes dendritic branching.Scientific reports · 2016Article
- PLD1 participates in BDNF-induced signalling in cortical neurons.Scientific reports · 2015Article
- The role of phospholipase D1 in liver fibrosis induced by dimethylnitrosamine in vivo.Digestive diseases and sciences · 2014Article
- Transcriptional Upregulation of Plasminogen Activator Inhibitor-1 in Rat Primary Astrocytes by a Proteasomal Inhibitor MG132.Biomolecules & therapeutics · 2013Article
- PLD1 Negatively Regulates Dendritic Branching.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Mammalian phospholipase D physiological and pathological roles.Acta physiologica (Oxford, England) · 2012Review
- Multipotent mesenchymal stromal cells increase tPA expression and concomitantly decrease PAI-1 expression in astrocytes through the sonic hedgehog signaling pathway after stroke (in vitro study).Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2011Article
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- Phospholipase D in brain function and Alzheimer's disease.Biochimica et biophysica acta · 2010Review
- Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice.Neurobiology of disease · 2010Article
- Phospholipase D1 is required for angiogenesis of intersegmental blood vessels in zebrafish.Developmental biology · 2009Article
- Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Temporal lobe epilepsy (TLE) is the most common form of epilepsy, affecting approximately 1-2% of the population. Seizure events resulting from TLE are characterized by aberrant hippocampal mossy fiber sprouting and plastic responses that affect brain function. Seizure susceptibility is modulated by the enzyme tissue plasminogen activator (tPA), the normal physiological role of which includes promotion of synaptic reorganization in the mossy fiber pathway by initiating a proteolytic cascade that cleaves extracellular matrix components and influences neurite extension. tPA is concentrated at and selectively secreted from growth cones during excitatory events. However, the mechanisms underlying tPA release during seizure-induced synaptogenesis are not well understood. We examine here potential roles for the signaling enzyme phospholipase D1 (PLD1), which promotes regulated exocytosis in non-CNS cell types, and which we previously demonstrated increases in expression in hippocampal neurons during seizure-induced mossy fiber sprouting. We now show that overexpression of wild-type PLD1 in cultured neurons promotes tPA release and tPA-dependent neurite extension, whereas overexpression of an inactive PLD1 allele or pharmacological inhibition of PLD1 inhibits tPA release. Similarly, viral delivery of wild-type PLD1 into the hippocampus facilitates tPA secretion and mossy fiber sprouting in a seizure-inducing model, whereas the inactive PLD1 allele inhibits tPA release and elicits blunted and abnormal mossy fiber extension similar to that observed for tPA-/- mice. Together, these findings secretion and thus mossy fiber extension in the setting of elevated suggest that PLD1 functions endogenously to regulate tPA-/- neuronal stimulation, such as that seen in TLE.
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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.