Evidence map›Paper›PMID 24431460›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014

Cognitive enhancing treatment with a PPARγ agonist normalizes dentate granule cell presynaptic function in Tg2576 APP mice.

Miroslav N Nenov, Fernanda Laezza, Sigmund J Haidacher, Yingxin Zhao, Rovshan G Sadygov, Jonathan M Starkey, Heidi Spratt, Bruce A Luxon, Kelly T Dineley, Larry Denner

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

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 5% 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.

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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

10 authors at 4 institutions in 4 countries.

Miroslav N NenovDepartment of Neurology, Department of Pharmacology and Toxicology, Department of Biochemistry and Molecular Biology, Department of Internal Medicine, Preventive Medicine and Community Health, Mitchell Center for Neurodegenerative Diseases, Center for Addiction Research, Center for Biomedical Engineering, and Sealy Center for Molecular Medicine, Institute for Translational Science, University of Texas Medical Branch, Galveston, Texas 77555.
Fernanda Laezza
Sigmund J Haidacher
Yingxin Zhao
Rovshan G Sadygov
Jonathan M Starkey
Heidi Spratt
Bruce A Luxon
Kelly T Dineley
Larry Denner
Laboratoire de Biochimie · FRAddiction Research Foundation · USThe University of Texas Medical Branch at Galveston · USGeneral Department of Preventive Medicine · VN

Funding

Mechanisms of PPAR-gamma Enhancement of Cognitive Function in Alzheimer's DiseaseR01AG031859 · NIA · UNIVERSITY OF TEXAS MED BR GALVESTON · PI DENNER, LARRY, DINELEY, KELLY T · 2009 to 2013
$1.6M
NIA NIH HHS AG031859NIA NIH HHS R01 AG031859
6 · The paper itself

Abstract

Hippocampal network hyperexcitability is considered an early indicator of Alzheimer's disease (AD) memory impairment. Some AD mouse models exhibit similar network phenotypes. In this study we focused on dentate gyrus (DG) granule cell spontaneous and evoked properties in 9-month-old Tg2576 mice that model AD amyloidosis and cognitive deficits. Using whole-cell patch-clamp recordings, we found that Tg2576 DG granule cells exhibited spontaneous EPSCs that were higher in frequency but not amplitude compared with wild-type mice, suggesting hyperactivity of DG granule cells via a presynaptic mechanism. Further support of a presynaptic mechanism was revealed by increased I-O relationships and probability of release in Tg2576 DG granule cells. Since we and others have shown that activation of the peroxisome proliferator-activated receptor gamma (PPARγ) axis improves hippocampal cognition in mouse models for AD as well as benefitting memory performance in some humans with early AD, we investigated how PPARγ agonism affected synaptic activity in Tg2576 DG. We found that PPARγ agonism normalized the I-O relationship of evoked EPSCs, frequency of spontaneous EPSCs, and probability of release that, in turn, correlated with selective expression of DG proteins essential for presynaptic SNARE function that are altered in patients with AD. These findings provide evidence that DG principal cells may contribute to early AD hippocampal network hyperexcitability via a presynaptic mechanism, and that hippocampal cognitive enhancement via PPARγ activation occurs through regulation of presynaptic vesicular proteins critical for proper glutamatergic neurotransmitter release, synaptic transmission, and short-term plasticity.

Indexed as

Amyloid beta-Protein PrecursorAnimalsDentate GyrusFemaleMaleMiceMice, Inbred C57BLMice, TransgenicNootropic AgentsOrgan Culture TechniquesPPAR gammaPresynaptic TerminalsProtein Interaction MapsProtein TransportRosiglitazoneThiazolidinedionesAmyloid beta-Protein PrecursorNootropic AgentsPPAR gammaRosiglitazoneThiazolidinedionesAlzheimer'sanimal modelmass spectrometrypatch clampSNARE proteinssynaptic plasticity

Identifiers

PMID24431460
PMCPMC3891946
OpenAlexW2045489354

What OpenQuestion holds

Textmetadata
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.