Evidence map›Paper›PMID 41839929›Full record

ArticleScientific reports2026

Increased type 3 deiodinase reduces hippocampal T3 signaling and is associated with cognitive impairment in a sporadic Alzheimer's disease animal model.

Rafael Aguiar Marschner, Rafael Teixeira Ribeiro, Vitor Gayger-Dias, Vanessa-Fernanda Da Silva, Simone Magagnin Wajner, Carlos-Alberto Gonçalves

Abstract read
In one paragraph

Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

6 authors.

Rafael Aguiar MarschnerPostgraduate Program in Biochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos Street, 2600, Laboratory 33., Porto Alegre, RS, 90035-003, Brazil. rafamarschner@gmail.com.
Rafael Teixeira RibeiroPostgraduate Program in Biochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos Street, 2600, Laboratory 33., Porto Alegre, RS, 90035-003, Brazil.
Vitor Gayger-DiasPostgraduate Program in Biochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos Street, 2600, Laboratory 33., Porto Alegre, RS, 90035-003, Brazil.
Vanessa-Fernanda Da SilvaPostgraduate Program in Biochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos Street, 2600, Laboratory 33., Porto Alegre, RS, 90035-003, Brazil.
Simone Magagnin WajnerEndocrine Division, Hospital de Clínicas de Porto Alegr, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Carlos-Alberto GonçalvesPostgraduate Program in Biochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos Street, 2600, Laboratory 33., Porto Alegre, RS, 90035-003, Brazil.

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico 302102/2022-1Conselho Nacional de Desenvolvimento Científico e Tecnológico , Brasil 171607/2023-6
6 · The paper itself

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β and tau pathology, neuroinflammation, oxidative stress, and cognitive decline. Emerging evidence indicates that thyroid hormone (TH) dysregulation may also contribute to AD pathogenesis, particularly through impaired hippocampal signaling. THs are crucial for neuronal metabolism, plasticity, and mitochondrial integrity, and their local availability is tightly controlled by deiodinases. This study investigated the role of type 3 deiodinase (D3) and its redox-dependent regulation via glutathione (GSH) in a streptozotocin (STZ)-induced model of sporadic AD. Male Wistar rats received intracerebroventricular STZ or vehicle and were evaluated 16 weeks later. STZ-treated rats exhibited significant deficits in short-term (p = 0.0090) and long-term (p = 0.0117) memory, accompanied by elevated hippocampal IL-6 and TNF-α (p < 0.0001), increased protein carbonylation (p = 0.0162), and depletion of GSH (p = 0.0326) and sulfhydryl groups (p = 0.0165). D3 mRNA (p < 0.0001) and protein (p = 0.0247) were upregulated, while T3-responsive genes Klf9 (p < 0.0001) and HR (p = 0.0353) were downregulated, indicating impaired TH signaling. Mitochondrial dysfunction was evidenced by reduced expression of Nrf1 (p = 0.0337), PGC-1α (p = 0.0035), Bcl2 (p = 0.0305), and COX4 (p = 0.0077), with increased CHOP (p = 0.0034), GRP78 (p < 0.0001), and ERK activation (p < 0.0001).Together, these findings demonstrate that inflammation- and redox-driven D3 upregulation decreases hippocampal T3 availability, disrupting TH signaling and promoting mitochondrial dysfunction and cognitive decline in sporadic AD.

Indexed as

Alzheimer DiseaseCognitive DysfunctionHippocampusIodide PeroxidaseTriiodothyronineAnimalsDisease Models, AnimalGlutathioneMaleOxidative StressRatsRats, WistarSignal TransductionStreptozocinGlutathioneIodide Peroxidaseiodothyronine deiodinase type IIIStreptozocinTriiodothyronineAlzheimer diseaseOxidative stressStreptozotocinType 3 deiodinase

Identifiers

PMID41839929
PMCPMC13125284

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.