Evidence map›Paper›PMID 35713704›Full record

ArticleActa neuropathologica2022

TDP-43 drives synaptic and cognitive deterioration following traumatic brain injury.

Fei Gao, Mei Hu, Jian Zhang, Jack Hashem, Chu Chen

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

Article in Acta neuropathologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 2 pooled it
5.5field-weighted citation impact, top 3% 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

31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 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

5 authors at 1 institution in 1 country.

Fei Gao *Department of Cellular and Integrative Physiology, Center for Biomedical Neuroscience, Joe R. and Teresa Lozano Long School of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, 78229, USA.
Mei Hu *Department of Cellular and Integrative Physiology, Center for Biomedical Neuroscience, Joe R. and Teresa Lozano Long School of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, 78229, USA.
Jian Zhang *Department of Cellular and Integrative Physiology, Center for Biomedical Neuroscience, Joe R. and Teresa Lozano Long School of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, 78229, USA.
Jack HashemDepartment of Cellular and Integrative Physiology, Center for Biomedical Neuroscience, Joe R. and Teresa Lozano Long School of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, 78229, USA.
Chu ChenDepartment of Cellular and Integrative Physiology, Center for Biomedical Neuroscience, Joe R. and Teresa Lozano Long School of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, 78229, USA. chenc7@uthscsa.edu.ORCID http://orcid.org/0000-0003-1287-8059
The University of Texas Health Science Center at San Antonio · US

Funding

Endocannabinoids in Neurodegenerative DiseasesR01NS076815 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI CHU CHEN · 2012 to 2026
$4.2M
Traumatic brain injury and Alzheimer's diseaseR01AG058621 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI CHEN, CHU · 2018 to 2022
$1.9M
Endocannabinoid Metabolism and Synaptic FunctionR01MH113535 · NIMH · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI CHEN, CHU · 2018 to 2022
$1.9M
NIA NIH HHS R01 AG058621NIMH NIH HHS R01 MH113535NINDS NIH HHS R01 NS076815
6 · The paper itself

Abstract

Traumatic brain injury (TBI) has been recognized as an important risk factor for Alzheimer's disease (AD). However, the molecular mechanisms by which TBI contributes to developing AD remain unclear. Here, we provide evidence that aberrant production of TDP-43 is a key factor in promoting AD neuropathology and synaptic and cognitive deterioration in mouse models of mild closed head injury (CHI). We observed that a single mild CHI is sufficient to exacerbate AD neuropathology and accelerate synaptic and cognitive deterioration in APP transgenic mice but repeated mild CHI are required to induce neuropathological changes and impairments in synaptic plasticity, spatial learning, and memory retention in wild-type animals. Importantly, these changes in animals exposed to a single or repeated mild CHI are alleviated by silencing of TDP-43 but reverted by rescue of the TDP-43 knockdown. Moreover, overexpression of TDP-43 in the hippocampus aggravates AD neuropathology and provokes cognitive impairment in APP transgenic mice, mimicking single mild CHI-induced changes. We further discovered that neuroinflammation triggered by TBI promotes NF-κB-mediated transcription and expression of TDP-43, which in turn stimulates tau phosphorylation and Aβ formation. Our findings suggest that excessive production of TDP-43 plays an important role in exacerbating AD neuropathology and in driving synaptic and cognitive declines following TBI.

Indexed as

Alzheimer DiseaseBrain Injuries, TraumaticCognitive DysfunctionAnimalsCognitionDisease Models, AnimalDNA-Binding ProteinsMiceMice, TransgenicDNA-Binding ProteinsTardbp protein, mouseMild closed head injuryNeurodegenerationNeuroinflammationSynaptic plasticityTau phosphorylationTDP-43Traumatic brain injury

Identifiers

PMID35713704
PMCPMC9945325
OpenAlexW4283034785

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.