ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.
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Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 240 citations in OpenAlex.
- Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases.International journal of molecular sciences · 2020Pooled it
- Cannabinoid tolerance relies on CBProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Increased Cannabinoid Receptor 1-Immunopositive Perisomatic Input of Principal Cells in Human Epileptic Patients in Focal Cortical Dysplasia Type IIB.International journal of molecular sciences · 2026Article
- Canine Idiopathic Epilepsy as a Natural Animal Model for Human Epilepsy: A Scoping Review Highlighting Metabolic Perspectives Beyond the Brain.Nutrients · 2026Article
- Cannabidiol in Neurology: Current Insights and Translational Perspectives.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Cannabinoids and Adverse Convulsive Effects: A Pharmacovigilance and Addictovigilance Analysis of Cases Reported in France.Fundamental & clinical pharmacology · 2025Article
- Article
- Dysregulation of the Cannabinoid System in Childhood Epilepsy: From Mechanisms to Therapy.International journal of molecular sciences · 2025Review
- Distribution of NECAB1-Positive Neurons in Normal and Epileptic Brain-Expression Changes in Temporal Lobe Epilepsy and Modulation by Levetiracetam and Brivaracetam.International journal of molecular sciences · 2025Article
- Absolute Number of Three Populations of Interneurons and All GABAergic Synapses in the Human Hippocampus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Anticonvulsant Effects of SyntheticMolecules (Basel, Switzerland) · 2025Article
- Adeno-Associated Viral Vectors in the Treatment of Epilepsy.International journal of molecular sciences · 2024Review
- Mapping dynamic molecular changes in hippocampal subregions after traumatic brain injury through spatial proteomics.Clinical proteomics · 2024Article
- Early endocannabinoid-mediated depolarization-induced suppression of excitation delays the appearance of the epileptic phenotype in synapsin II knockout mice.Cellular and molecular life sciences : CMLS · 2024Article
- Article
- Increased hippocampal cannabinoid 1 receptor expression is associated with protection from severe seizures in pregnant mice with reduced uterine perfusion pressure.Journal of neuroscience research · 2023Article
- Control of a hippocampal recurrent excitatory circuit by cannabinoid receptor-interacting protein Gap43.Nature communications · 2023Article
- Hippocampal expression of the cannabinoid receptor type 1 in canine epilepsy.Scientific reports · 2023Article
- Antitumor Potential of Antiepileptic Drugs in Human Glioblastoma: Pharmacological Targets and Clinical Benefits.Biomedicines · 2023Review
- Endocannabinoids at the synapse and beyond: implications for neuropsychiatric disease pathophysiology and treatment.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Endocannabinoid signaling is a key regulator of synaptic neurotransmission throughout the brain. Compelling evidence shows that its perturbation leads to development of epileptic seizures, thus indicating that endocannabinoids play an intrinsic protective role in suppressing pathologic neuronal excitability. To elucidate whether long-term reorganization of endocannabinoid signaling occurs in epileptic patients, we performed comparative expression profiling along with quantitative electron microscopic analysis in control (postmortem samples from subjects with no signs of neurological disorders) and epileptic (surgically removed from patients with intractable temporal lobe epilepsy) hippocampal tissue. Quantitative PCR measurements revealed that CB(1) cannabinoid receptor mRNA was downregulated to one-third of its control value in epileptic hippocampus. Likewise, the cannabinoid receptor-interacting protein-1a mRNA was decreased, whereas 1b isoform levels were unaltered. Expression of diacylglycerol lipase-alpha, an enzyme responsible for 2-arachidonoylglycerol synthesis, was also reduced by approximately 60%, whereas its related beta isoform levels were unchanged. Expression level of N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D and fatty acid amide hydrolase, metabolic enzymes of anandamide, and 2-arachidonoylglycerol's degrading enzyme monoacylglycerol lipase did not change. The density of CB(1) immunolabeling was also decreased in epileptic hippocampus, predominantly in the dentate gyrus, where quantitative electron microscopic analysis did not reveal changes in the ratio of CB(1)-positive GABAergic boutons, but uncovered robust reduction in the fraction of CB(1)-positive glutamatergic axon terminals. These findings show that a neuroprotective machinery involving endocannabinoids is impaired in epileptic human hippocampus and imply that downregulation of CB(1) receptors and related molecular components of the endocannabinoid system may facilitate the deleterious effects of increased network excitability.
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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.