Evidence map›Paper›PMID 31705957›Full record

ArticleMolecular and cellular neurosciences2020

Overexpression of human wtTDP-43 causes impairment in hippocampal plasticity and behavioral deficits in CAMKII-tTa transgenic mouse model.

Zainuddin Quadri, Nicholas Johnson, Frank Zamudio, Abraian Miller, Melinda Peters, Shayna Smeltzer, Jerry B Hunt, Steven B Housley, Breanna Brown, Susan Kraner and 5 more

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

Article in Molecular and cellular neurosciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.8field-weighted citation impact, top 26% 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

7 citing papers in PubMed, 10 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

15 authors at 3 institutions in 1 country.

Zainuddin QuadriDepartment of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA.
Nicholas JohnsonDepartment of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA.
Frank ZamudioDepartment of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA.
Abraian MillerDepartment of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA.
Melinda PetersByrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA; Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Shayna SmeltzerDepartment of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA.
Jerry B HuntDepartment of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA.
Steven B HousleyByrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA; Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Breanna BrownDepartment of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA.
Susan KranerSanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington, KY, USA.
Christopher M NorrisSanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington, KY, USA.
Kevin NashByrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA; Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Edwin WeeberByrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA; Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Daniel C LeeDepartment of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA.
Maj-Linda B SelenicaDepartment of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA. Electronic address: mselenica@usf.edu.
USF Health Byrd Alzheimer's Institute · USUniversity of South Florida · USUniversity of Kentucky · US

Funding

Calcineurin and inflammatory signaling processes in aging and Alzheimer's DiseaseRF1AG027297 · NIA · UNIVERSITY OF KENTUCKY · PI NORRIS, CHRISTOPHER MARK · 2018 to 2022
$2.6M
NIA NIH HHS RF1 AG027297
6 · The paper itself

Abstract

aimsThe current study utilizes the adeno-associated viral gene transfer system in the CAMKIIα-tTA mouse model to overexpress human wild type TDP-43 (wtTDP-43) and α-synuclein (α-Syn) proteins. The co-existence of these proteins is evident in the pathology of neurodegenerative disorders such as frontotemporal lobar degeneration (FTLD), Parkinson disease (PD), and dementia with Lewy bodies (DLB).

methodsThe novel bicistronic recombinant adeno-associated virus (rAAV) serotype 9 drives wtTDP-43 and α-Syn expression in the hippocampus via "TetO" CMV promoter. Behavior, electrophysiology, and biochemical and histological assays were used to validate neuropathology.

resultsWe report that overexpression of wtTDP-43 but not α-Syn contributes to hippocampal CA2-specific pyramidal neuronal loss and overall hippocampal atrophy. Further, we report a reduction of hippocampal long-term potentiation and decline in learning and memory performance of wtTDP-43 expressing mice. Elevated wtTDP-43 levels induced selective degeneration of Purkinje cell protein 4 (PCP-4) positive neurons while both wtTDP-43 and α-Syn expression reduced subsets of the glutamate receptor expression in the hippocampus.

conclusionsOverall, our findings suggest the significant vulnerability of hippocampal neurons toward elevated wtTDP-43 levels possibly via PCP-4 and GluR-dependent calcium signaling pathways. Further, we report that wtTDP-43 expression induced selective CA2 subfield degeneration, contributing to the deterioration of the hippocampal-dependent cognitive phenotype.

Indexed as

Long-Term PotentiationMemoryalpha-SynucleinAnimalsCA2 Region, HippocampalCalcium-Calmodulin-Dependent Protein Kinase Type 2DNA-Binding ProteinsGuanine Nucleotide Exchange FactorsHumansMaze LearningMiceNeuropeptidesPyramidal CellsReceptors, Glutamatealpha-SynucleinCalcium-Calmodulin-Dependent Protein Kinase Type 2DNA-Binding ProteinsGuanine Nucleotide Exchange FactorsNeuropeptidesPcp2 protein, mouseReceptors, GlutamateTARDBP protein, humanALSCA2FTLDGlutamate receptorHippocampusLearningPCP-4Synaptic plasticityTDP-43α-Synuclein

Identifiers

PMID31705957
PMCPMC7505208
OpenAlexW2987896975

What OpenQuestion holds

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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.