Evidence map›Paper›PMID 39547478›Full record

ArticleNeurobiology of disease2024

PTEN deletion in the adult dentate gyrus induces epilepsy.

Jennifer M Yonan, Kevin D Chen, Tallie Z Baram, Oswald Steward

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Jennifer M YonanReeve-Irvine Research Center, Gillespie Neuroscience Research Facility, 837 Health Sciences Road, University of California at Irvine, Irvine, CA 92697, USA; Department of Anatomy & Neurobiology, University of California at Irvine, Irvine, CA 92697, USA; University of California at Irvine School of Medicine, Irvine, CA, 92697, USA.
Kevin D ChenDepartment of Neurology, University of California at Irvine, Irvine, CA 92697, USA.
Tallie Z BaramDepartment of Anatomy & Neurobiology, University of California at Irvine, Irvine, CA 92697, USA; Department of Pediatrics, University of California at Irvine, Irvine, CA 92697, USA; Department of Neurology, University of California at Irvine, Irvine, CA 92697, USA; University of California at Irvine School of Medicine, Irvine, CA, 92697, USA.
Oswald StewardReeve-Irvine Research Center, Gillespie Neuroscience Research Facility, 837 Health Sciences Road, University of California at Irvine, Irvine, CA 92697, USA; Department of Anatomy & Neurobiology, University of California at Irvine, Irvine, CA 92697, USA; Department of Neurobiology & Behavior, University of California at Irvine, Irvine, CA 92697, USA; Department of Neurosurgery, University of California at Irvine, Irvine, CA 92697, USA; Center for the Neurobiology of Learning and Memory, University of California at Irvine, Irvine, CA 92697, USA; University of California at Irvine School of Medicine, Irvine, CA, 92697, USA. Electronic address: osteward@uci.edu.

Funding

Epilepsy Research Training ProgramT32NS045540 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI Tallie Z. Baram, Robert F Hunt · 2003 to 2026
$4.9M
Cognitive Deficits After Experimental Febrile Seizures: Neurobiology & BiomarkersR01NS108296 · NINDS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI BARAM, TALLIE Z., HOLMES, GREGORY L. · 2018 to 2022
$2.6M
Mechanisms of Corticospinal Tract RegenerationR01NS108189 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI STEWARD, OSWALD · 2019 to 2022
$2.3M
NINDS NIH HHS R01 NS108189NINDS NIH HHS R01 NS108296NINDS NIH HHS T32 NS045540
6 · The paper itself

Abstract

Embryonic and early postnatal promotor-driven deletion of the phosphatase and tensin homolog (PTEN) gene results in neuronal hypertrophy, hyperexcitable circuitry and development of spontaneous seizures in adulthood. We previously documented that focal, vector-mediated PTEN deletion in mature granule cells of the adult dentate gyrus triggers dramatic growth of cell bodies, dendrites, and axons, similar to that seen with early postnatal PTEN deletion. Here, we assess the functional consequences of focal, adult PTEN deletion, focusing on its pro-epileptogenic potential. PTEN deletion was accomplished by injecting AAV-Cre either bilaterally or unilaterally into the dentate gyrus of double transgenic PTEN-floxed, ROSA-reporter mice. Hippocampal recording electrodes were implanted for continuous digital EEG with concurrent video recordings in the home cage. Electrographic seizures and epileptiform spikes were assessed manually by two investigators, and correlated with concurrent videos. Spontaneous electrographic and behavioral seizures appeared after focal PTEN deletion in adult dentate granule cells, commencing around 2 months post-AAV-Cre injection. Seizures occurred in the majority of mice with unilateral or bilateral PTEN deletion and led to death in several cases. PTEN-deletion provoked epilepsy was not associated with apparent hippocampal neuron death; supra-granular mossy fiber sprouting was observed in a few mice. In summary, focal, unilateral deletion of PTEN in the adult dentate gyrus suffices to provoke time-dependent emergence of a hyperexcitable circuit generating hippocampus-origin, generalizing spontaneous seizures, providing a novel model for studies of adult-onset epileptogenesis.

Indexed as

Dentate GyrusEpilepsyMice, TransgenicPTEN PhosphohydrolaseAnimalsDisease Models, AnimalElectroencephalographyGene DeletionMaleMiceMice, Inbred C57BLNeuronsPTEN PhosphohydrolasePten protein, mouseDentate gyrusEEGEpilepsyGranule cellsHippocampusmTORPTENSeizure

Identifiers

PMID39547478
PMCPMC11756830

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Registered trials

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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.