ArticleThe Journal of comparative neurology2015
Blockade of excitatory synaptogenesis with proximal dendrites of dentate granule cells following rapamycin treatment in a mouse model of temporal lobe epilepsy.
Article in The Journal of comparative neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Emerging Molecular Targets for Anti-Epileptogenic and Epilepsy Modifying Drugs.International journal of molecular sciences · 2023Review
- Impact of Raptor and Rictor Deletion on Hippocampal Pathology Following Status Epilepticus.Journal of molecular neuroscience : MN · 2022Article
- Genetic Inhibition of Plppr5 Aggravates Hypoxic-Ischemie-Induced Cortical Damage and Excitotoxic Phenotype.Frontiers in neuroscience · 2022Article
- Astrocyte Role in Temporal Lobe Epilepsy and Development of Mossy Fiber Sprouting.Frontiers in cellular neuroscience · 2021Review
- Hippocampal granule cell dispersion: a non-specific finding in pediatric patients with no history of seizures.Acta neuropathologica communications · 2020Article
- Proportional loss of parvalbumin-immunoreactive synaptic boutons and granule cells from the hippocampus of sea lions with temporal lobe epilepsy.The Journal of comparative neurology · 2019Article
- Editorial: The Developmental Seizure-Induced Hippocampal Mossy Fiber Sprouting: Target for Epilepsy Therapies?Frontiers in neurology · 2019Article
- Mechanistic target of rapamycin complex 1 and 2 in human temporal lobe epilepsy.Annals of neurology · 2018Article
- Signaling Pathways and Cellular Mechanisms Regulating Mossy Fiber Sprouting in the Development of Epilepsy.Frontiers in neurology · 2018Review
- Total Number Is Important: Using the Disector Method in Design-Based Stereology to Understand the Structure of the Rodent Brain.Frontiers in neuroanatomy · 2018Review
- Is Mossy Fiber Sprouting a Potential Therapeutic Target for Epilepsy?Frontiers in neurology · 2018Review
- Combining Constitutively Active Rheb Expression and Chondroitinase Promotes Functional Axonal Regeneration after Cervical Spinal Cord Injury.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Impact of rapamycin on status epilepticus induced hippocampal pathology and weight gain.Experimental neurology · 2016Article
- Expressing Constitutively Active Rheb in Adult Dorsal Root Ganglion Neurons Enhances the Integration of Sensory Axons that Regenerate Across a Chondroitinase-Treated Dorsal Root Entry Zone Following Dorsal Root Crush.Frontiers in molecular neuroscience · 2016Article
- Surviving mossy cells enlarge and receive more excitatory synaptic input in a mouse model of temporal lobe epilepsy.Hippocampus · 2015Article
- PTEN deletion from adult-generated dentate granule cells disrupts granule cell mossy fiber axon structure.Neurobiology of disease · 2015Article
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Authors and funding
3 authors at 2 institutions in 1 country.
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Abstract
Inhibiting the mammalian target of rapamycin (mTOR) signaling pathway with rapamycin blocks granule cell axon (mossy fiber) sprouting after epileptogenic injuries, including pilocarpine-induced status epilepticus. However, it remains unclear whether axons from other types of neurons sprout into the inner molecular layer and synapse with granule cell dendrites despite rapamycin treatment. If so, other aberrant positive-feedback networks might develop. To test this possibility stereological electron microscopy was used to estimate the numbers of excitatory synapses in the inner molecular layer per hippocampus in pilocarpine-treated control mice, in mice 5 days after pilocarpine-induced status epilepticus, and after status epilepticus and daily treatment beginning 24 hours later with rapamycin or vehicle for 2 months. The optical fractionator method was used to estimate numbers of granule cells in Nissl-stained sections so that numbers of excitatory synapses in the inner molecular layer per granule cell could be calculated. Control mice had an average of 2,280 asymmetric synapses in the inner molecular layer per granule cell, which was reduced to 63% of controls 5 days after status epilepticus, recovered to 93% of controls in vehicle-treated mice 2 months after status epilepticus, but remained at only 63% of controls in rapamycin-treated mice. These findings reveal that rapamycin prevented excitatory axons from synapsing with proximal dendrites of granule cells and raise questions about the recurrent excitation hypothesis of temporal lobe epilepsy.
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Registered trials
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