ArticlePloS one2010
AAV vector-mediated overexpression of CB1 cannabinoid receptor in pyramidal neurons of the hippocampus protects against seizure-induced excitoxicity.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 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
- Exploring Linalool-Based Phytotherapy for Excitatory/Inhibitory Imbalance in Alzheimer's Disease: A Review of Lavender and Cannabis Therapeutic Effects on Sleep, Seizures, and Cognition.Phytotherapy research : PTR · 2026Review
- Cannabinoid Receptor 1: The Neural Gatekeeper of Health and Disease.Current neurovascular research · 2025Review
- Adeno-Associated Viral Vectors in the Treatment of Epilepsy.International journal of molecular sciences · 2024Review
- 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
- Anxiety Modulation by Cannabinoids-The Role of Stress Responses and Coping.International journal of molecular sciences · 2023Review
- Control of a hippocampal recurrent excitatory circuit by cannabinoid receptor-interacting protein Gap43.Nature communications · 2023Article
- The Role of Glutamate Receptors in Epilepsy.Biomedicines · 2023Review
- mTORC1 regulates high levels of protein synthesis in retinal ganglion cells of adult mice.The Journal of biological chemistry · 2022Article
- The Endocannabinoid System in Glial Cells and Their Profitable Interactions to Treat Epilepsy: Evidence from Animal Models.International journal of molecular sciences · 2021Review
- Regulation of stress-provoked aggressive behavior using endocannabinoids.Neurobiology of stress · 2021Article
- Cannabinoid CB1 receptor in dorsal telencephalic glutamatergic neurons drives overconsumption of palatable food and obesity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Review
- Endocannabinoid-Mediated Control of Neural Circuit Excitability and Epileptic Seizures.Frontiers in neural circuits · 2021Review
- Distribution of the Cannabinoid Receptor Type 1 in the Brain of the Genetically Audiogenic Seizure-Prone Hamster GASH/Sal.Frontiers in behavioral neuroscience · 2021Article
- Neural Stem Cells and Cannabinoids in the Spotlight as Potential Therapy for Epilepsy.International journal of molecular sciences · 2020Review
- Development and Validation of CRISPR Activator Systems for Overexpression of CB1 Receptors in Neurons.Frontiers in molecular neuroscience · 2020Article
- Druggable targets of the endocannabinoid system: Implications for the treatment of HIV-associated neurocognitive disorder.Brain research · 2019Review
- Impaired anandamide/palmitoylethanolamide signaling in hippocampal glutamatergic neurons alters synaptic plasticity, learning, and emotional responses.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- Gadd45α modulates aversive learning through post-transcriptional regulation of memory-related mRNAs.EMBO reports · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The CB1 cannabinoid receptor is the most abundant G-protein coupled receptor in the brain and a key regulator of neuronal excitability. There is strong evidence that CB1 receptor on glutamatergic hippocampal neurons is beneficial to alleviate epileptiform seizures in mouse and man. Therefore, we hypothesized that experimentally increased CB1 gene dosage in principal neurons would have therapeutic effects in kainic acid (KA)-induced hippocampal pathogenesis. Here, we show that virus-mediated conditional overexpression of CB1 receptor in pyramidal and mossy cells of the hippocampus is neuroprotective and moderates convulsions in the acute KA seizure model in mice. We introduce a recombinant adeno-associated virus (AAV) genome with a short stop element flanked by loxP sites, for highly efficient attenuation of transgene expression on the transcriptional level. The presence of Cre-recombinase is strictly necessary for expression of reporter proteins or CB1 receptor in vitro and in vivo. Transgenic CB1 receptor immunoreactivity is targeted to glutamatergic neurons after stereotaxic delivery of AAV to the dorsal hippocampus of the driver mice NEX-cre. Increased CB1 receptor protein levels in hippocampal lysates of AAV-treated Cre-mice is paralleled by enhanced cannabinoid-induced G-protein activation. KA-induced seizure severity and mortality is reduced in CB1 receptor overexpressors compared with AAV-treated control animals. Neuronal damage in the hippocampal CA3 field is specifically absent from AAV-treated Cre-transgenics, but evident throughout cortical areas of both treatment groups. Our data provide further evidence for a role of increased CB1 signaling in pyramidal hippocampal neurons as a safeguard against the adverse effects of excessive excitatory network activity.
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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.