Evidence map›Paper›PMID 37700086›Full record

ArticlePsychopharmacology2023

Pharmacological inhibition of plasminogen activator inhibitor-1 prevents memory deficits and reduces neuropathology in APP/PS1 mice.

Guadalupe Rodriguez, Mesut Eren, Isabel Haupfear, Kirsten L Viola, Erika N Cline, Toshio Miyata, William L Klein, Douglas E Vaughan, Hongxin Dong

Abstract read
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Article in Psychopharmacology, 2023. 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
1.8field-weighted citation impact, top 15% 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

9 authors at 2 institutions in 2 countries.

Guadalupe RodriguezDepartment of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Ward 7-103, Chicago, IL, 60611, USA.
Mesut ErenDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
Isabel HaupfearDepartment of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Ward 7-103, Chicago, IL, 60611, USA.
Kirsten L ViolaDepartment of Neurobiology, Northwestern University, 2205 Tech Drive, Hogan 4-160, Evanston, IL, 60208, USA.
Erika N ClineDepartment of Neurobiology, Northwestern University, 2205 Tech Drive, Hogan 4-160, Evanston, IL, 60208, USA.
Toshio MiyataDepartment of Molecular Medicine and Therapy, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
William L KleinDepartment of Neurobiology, Northwestern University, 2205 Tech Drive, Hogan 4-160, Evanston, IL, 60208, USA.
Douglas E VaughanDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
Hongxin DongDepartment of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Ward 7-103, Chicago, IL, 60611, USA. h-dong@northwestern.edu.ORCID http://orcid.org/0000-0002-2469-070X
Northwestern University · USTohoku University · JP

Funding

Evolutionary Advantage of Heterozygous PAI-1 Deficiency in HumansR56AG077278 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI VAUGHAN, DOUGLAS E · 2022 to 2022
$300k
NIA NIH HHS R56 AG077278
6 · The paper itself

Abstract

rationaleExtracellular proteolytic activity plays an important role in memory formation and the preservation of cognitive function. Previous studies have shown increased levels of plasminogen activator inhibitor-1 (PAI-1) in the brain of mouse models of Alzheimer's disease (AD) and plasma of AD patients, associated with memory and cognitive decline; however, the exact function of PAI-1 in AD onset and progression is largely unclear.

objectiveIn this study, we evaluated a novel PAI-1 inhibitor, TM5A15, on its ability to prevent or reverse memory deficits and decrease Aβ levels and plaque deposition in APP/PS1 mice.

methodsWe administered TM5A15 mixed in a chow diet to 3-month and 9-month-old APP/PS1 mice before and after neuropathological changes were distinguishable. We then evaluated the effects of TM5A15 on memory function and neuropathology at 9 months and 18 months of age.

resultsIn the younger mice, 6 months of TM5A15 treatment protected against recognition and short-term working memory impairment. TM5A15 also decreased oligomer levels and amyloid plaques, and increased mBDNF expression in APP/PS1 mice at 9 months of age. In aged mice, 9 months of TM5A15 treatment did not significantly improve memory function nor decrease amyloid plaques. However, TM5A15 treatment showed a trend in decreasing oligomer levels in APP/PS1 mice at 18 months of age.

conclusionOur results suggest that PAI-1 inhibition could improve memory function and reduce the accumulation of amyloid levels in APP/PS1 mice. Such effects are more prominent when TM5A15 is administered before advanced AD pathology and memory deficits occur.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsDisease Models, AnimalHumansInfantMemory DisordersMiceMice, TransgenicPlaque, AmyloidPlasminogen Activator Inhibitor 1Presenilin-1Amyloid beta-PeptidesAmyloid beta-Protein PrecursorPlasminogen Activator Inhibitor 1Presenilin-1Alzheimer’s diseaseBrain agingPlasminogen activator inhibitor-1Plasmin systemTM5A15

Identifiers

PMID37700086
OpenAlexW4386648320

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.