Evidence map›Paper›PMID 29551491›Full record

ArticleNeuron2018

Nav1.1-Overexpressing Interneuron Transplants Restore Brain Rhythms and Cognition in a Mouse Model of Alzheimer's Disease.

Magdalena Martinez-Losa, Tara E Tracy, Keran Ma, Laure Verret, Alexandra Clemente-Perez, Abdullah S Khan, Inma Cobos, Kaitlyn Ho, Li Gan, Lennart Mucke and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
144citing papers in PubMed, 2 pooled it
9.1field-weighted citation impact, top 1% of its field
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

144 citing papers in PubMed, 2 syntheses or guidelines pooled it, 240 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. mTORC2-NaChannels (Austin, Tex.) · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article

84 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

Magdalena Martinez-LosaGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, CA 94158, USA; Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, CSIC, Seville 41092, Spain.
Tara E TracyGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, CA 94158, USA.
Keran MaGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, CA 94158, USA.
Laure VerretGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, CA 94158, USA.
Alexandra Clemente-PerezGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, CA 94158, USA.
Abdullah S KhanGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
Inma CobosGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA.
Kaitlyn HoGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
Li GanGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, CA 94158, USA.
Lennart MuckeGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, CA 94158, USA.
Manuel Alvarez-DoladoGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, CSIC, Seville 41092, Spain; University Pablo de Olavide, Seville 41013, Spain. Electronic address: manuel.alvarez@cabimer.es.
Jorge J PalopGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, CA 94158, USA. Electronic address: jorge.palop@gladstone.ucsf.edu.
Gladstone Institutes · USUniversity of California, San Francisco · USCentro Andaluz de Biología Molecular y Medicina Regenerativa · ES

Funding

Project 3: Autophagy dysfunction and neuronal activity in FTDU54NS100717 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI CUERVO, ANA MARIA · 2016 to 2020
$10.8M
Roles of Amyloid Precursor Protein and its Metabolites in Neuronal ImpairmentR01NS041787 · NINDS · J. DAVID GLADSTONE INSTITUTES · PI MUCKE, LENNART · 2001 to 2015
$6.9M
Behavioral CoreP30NS065780 · NINDS · J. DAVID GLADSTONE INSTITUTES · PI MUCKE, LENNART · 2011 to 2015
$4.0M
Tau acetylation in Alzheimer's diseaseR01AG054214 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI GAN, LI · 2017 to 2021
$3.3M
Molecular mechanisms in progranulin deficient frontotemporal dementiaR01AG051390 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI GAN, LI · 2015 to 2019
$2.5M
EXTRAMULAR RESEARCH FACILITIES CONSTRUCTIONC06RR018928 · NCRR · J. DAVID GLADSTONE INSTITUTES · PI MAHLEY, ROBERT W. · 2003 to 2003
$2.1M
SIRT1 Limits Microglial Toxicity in Alzheimer's DiseaseR01AG036884 · NIA · J. DAVID GLADSTONE INSTITUTES · PI GAN, LI · 2012 to 2016
$2.0M
Restoring Brain Functions in Alzheimer Models with Interneuron TransplantsR01AG047313 · NIA · J. DAVID GLADSTONE INSTITUTES · PI PALOP, JORGE J · 2014 to 2018
$1.9M
The Role of Cathepsin B and Cystatin C in Alzheimer's DiseaseR01AG030207 · NIA · J. DAVID GLADSTONE INSTITUTES · PI GAN, LI · 2010 to 2014
$1.9M
Pathogenic events triggered by tau acetylation in neurodegenerative tauopathyF32AG043301 · NIA · J. DAVID GLADSTONE INSTITUTES · PI TRACY, TARA · 2012 to 2014
$156k
NCRR NIH HHS C06 RR018928NIA NIH HHS F32 AG043301NIA NIH HHS R01 AG030207NIA NIH HHS R01 AG036884NIA NIH HHS R01 AG047313NIA NIH HHS R01 AG051390NIA NIH HHS R01 AG054214NINDS NIH HHS P30 NS065780NINDS NIH HHS R01 NS041787NINDS NIH HHS U54 NS100717
6 · The paper itself

Abstract

Inhibitory interneurons regulate the oscillatory rhythms and network synchrony that are required for cognitive functions and disrupted in Alzheimer's disease (AD). Network dysrhythmias in AD and multiple neuropsychiatric disorders are associated with hypofunction of Nav1.1, a voltage-gated sodium channel subunit predominantly expressed in interneurons. We show that Nav1.1-overexpressing, but not wild-type, interneuron transplants derived from the embryonic medial ganglionic eminence (MGE) enhance behavior-dependent gamma oscillatory activity, reduce network hypersynchrony, and improve cognitive functions in human amyloid precursor protein (hAPP)-transgenic mice, which simulate key aspects of AD. Increased Nav1.1 levels accelerated action potential kinetics of transplanted fast-spiking and non-fast-spiking interneurons. Nav1.1-deficient interneuron transplants were sufficient to cause behavioral abnormalities in wild-type mice. We conclude that the efficacy of interneuron transplantation and the function of transplanted cells in an AD-relevant context depend on their Nav1.1 levels. Disease-specific molecular optimization of cell transplants may be required to ensure therapeutic benefits in different conditions.

Indexed as

Action PotentialsAlzheimer DiseaseAnimalsBrainBrain WavesCognitionDisease Models, AnimalGene ExpressionHippocampusHumansInterneuronsLocomotionMaze LearningMiceMice, TransgenicNAV1.1 Voltage-Gated Sodium ChannelNAV1.1 Voltage-Gated Sodium ChannelScn1a protein, mousecell therapyEEGepilepticGABAergiclearning and memoryoscillationsparvalbuminScn1aseizuressomatostatin

Identifiers

PMID29551491
PMCPMC5886814
OpenAlexW2790954104

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.