Evidence map›Paper›PMID 42410183›Full record

ArticleMolecular neurobiology2026

Chronic Lithium Exposure Reshapes PI3K-mTOR-linked Proteostatic Networks in the Hippocampus of an Alzheimer's Disease Mouse Model.

Caíque de Oliveira Portugal Couto, Maria Luiza Hass das Eiras, João Lucas Juliao de Morais, Carlos Wagner Leal Cordeiro Júnior, Orestes Vicente Forlenza, Vanessa de Jesus Rodrigues de Paula

Abstract read
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Article in Molecular neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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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

0 citing papers in PubMed.

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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

6 authors.

Caíque de Oliveira Portugal Couto *Neuroscience Laboratory LIM 27, Institute of Psychiatry of the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo, Rua Doutor Ovídio Pires de Campos, 785, Cerqueira César, São Paulo, 05403-903, Brazil.ORCID http://orcid.org/0000-0001-5447-3880
Maria Luiza Hass das Eiras *Neuroscience Laboratory LIM 27, Institute of Psychiatry of the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo, Rua Doutor Ovídio Pires de Campos, 785, Cerqueira César, São Paulo, 05403-903, Brazil.ORCID http://orcid.org/0009-0008-1546-7590
João Lucas Juliao de MoraisNeuroscience Laboratory LIM 27, Institute of Psychiatry of the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo, Rua Doutor Ovídio Pires de Campos, 785, Cerqueira César, São Paulo, 05403-903, Brazil.ORCID http://orcid.org/0009-0000-2111-2018
Carlos Wagner Leal Cordeiro JúniorNeuroscience Laboratory LIM 27, Institute of Psychiatry of the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo, Rua Doutor Ovídio Pires de Campos, 785, Cerqueira César, São Paulo, 05403-903, Brazil.ORCID http://orcid.org/0000-0002-4943-8949
Orestes Vicente ForlenzaNeuroscience Laboratory LIM 27, Institute of Psychiatry of the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo, Rua Doutor Ovídio Pires de Campos, 785, Cerqueira César, São Paulo, 05403-903, Brazil.ORCID http://orcid.org/0000-0002-6962-5899
Vanessa de Jesus Rodrigues de PaulaNeuroscience Laboratory LIM 27, Institute of Psychiatry of the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo, Rua Doutor Ovídio Pires de Campos, 785, Cerqueira César, São Paulo, 05403-903, Brazil. vanessaj@usp.br.ORCID http://orcid.org/0000-0002-2054-6356

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β deposition, tau pathology, and alterations in signaling pathways involved in neuronal survival and protein homeostasis. Lithium has been suggested as a potential neuroprotective treatment, but the molecular mechanisms associated with its long-term effects are still not fully understood. In this study, we investigated the effects of chronic lithium treatment on hippocampal proteins associated with PI3K-related signaling in triple-transgenic Alzheimer's disease (3xTg-AD) mice. Wild-type and transgenic animals received either a lower or higher lithium dose for eight months. Hippocampal samples were analyzed by LC-MS/MS proteomics followed by protein interaction and functional enrichment analyses. From a total of 7768 identified proteins, bioinformatic analyses identified 157 proteins shared between APP-, MAPT-, and PI3K-associated datasets. Further network analyses identified 18 proteins related to PI3K signaling, including seven proteins shared among all three datasets: FKBP1A, HSPA1B, HSPA8, RAS-related proteins, RPL13, RPL19, and RPL24. These proteins are associated with protein folding, translation regulation, cellular stress responses, and signaling pathways. Chronic lithium treatment was associated with changes in the expression of these proteins in both wild-type and transgenic animals. The observed effects differed between the two lithium concentrations tested and did not follow a simple linear pattern. Our findings suggest that long-term lithium exposure is associated with changes in molecular networks related to proteostasis and translational regulation in the hippocampus. Although additional studies are needed to better understand the mechanisms involved, these results provide a proteomic framework for investigating lithium-sensitive pathways that may be relevant to Alzheimer's disease.

Indexed as

Alzheimer DiseaseHippocampusLithiumPhosphatidylinositol 3-KinasesTOR Serine-Threonine KinasesAnimalsDisease Models, AnimalMiceMice, TransgenicProtein Interaction MapsProteomicsSignal TransductionLithiumPhosphatidylinositol 3-KinasesTOR Serine-Threonine KinasesAlzheimer's diseaseLithiumNeuroplasticityOntological pathwaysPhosphatidylinositol-3-kinase

Identifiers

PMID42410183
PMCPMC13337883

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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 Socratic graph.