Evidence map›Paper›PMID 38350966›Full record

ArticleBiology of sex differences2024

Nrf2 activation rescues stress-induced depression-like behaviour and inflammatory responses in male but not female rats.

Ryan T McCallum, Rachel-Karson Thériault, Joshua D Manduca, Isaac S B Russell, Angel M Culmer, Janan Shoja Doost, Tami A Martino, Melissa L Perreault

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biology of sex differences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

10 citing papers in PubMed, 17 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Ryan T McCallumDepartment of Biomedical Sciences, University of Guelph, 50 Stone Rd. E., Guelph, ON, N1G 2W1, Canada.
Rachel-Karson ThériaultDepartment of Biomedical Sciences, University of Guelph, 50 Stone Rd. E., Guelph, ON, N1G 2W1, Canada.
Joshua D ManducaDepartment of Biomedical Sciences, University of Guelph, 50 Stone Rd. E., Guelph, ON, N1G 2W1, Canada.
Isaac S B RussellDepartment of Biomedical Sciences, University of Guelph, 50 Stone Rd. E., Guelph, ON, N1G 2W1, Canada.
Angel M CulmerDepartment of Biomedical Sciences, University of Guelph, 50 Stone Rd. E., Guelph, ON, N1G 2W1, Canada.
Janan Shoja DoostDepartment of Biomedical Sciences, University of Guelph, 50 Stone Rd. E., Guelph, ON, N1G 2W1, Canada.
Tami A MartinoDepartment of Biomedical Sciences, University of Guelph, 50 Stone Rd. E., Guelph, ON, N1G 2W1, Canada.
Melissa L PerreaultDepartment of Biomedical Sciences, University of Guelph, 50 Stone Rd. E., Guelph, ON, N1G 2W1, Canada. perreaum@uoguelph.ca.ORCID 0000-0002-5775-8950
University of Guelph · CA

Funding

Institute of Neurosciences, Mental Health and Addiction 450186
6 · The paper itself

Abstract

backgroundMajor depressive disorder (MDD) is a recurring affective disorder that is two times more prevalent in females than males. Evidence supports immune system dysfunction as a major contributing factor to MDD, notably in a sexually dimorphic manner. Nuclear factor erythroid 2-related factor 2 (Nrf2), a regulator of antioxidant signalling during inflammation, is dysregulated in many chronic inflammatory disorders; however, its role in depression and the associated sex differences have yet to be explored. Here, we investigated the sex-specific antidepressant and immunomodulatory effects of the potent Nrf2 activator dimethyl fumarate (DMF), as well as the associated gene expression profiles.

methodsMale and female rats were treated with vehicle or DMF (25 mg/kg) whilst subjected to 8 weeks of chronic unpredictable stress. The effect of DMF treatment on stress-induced depression- and anxiety-like behaviours, as well as deficits in recognition and spatial learning and memory were then assessed. Sex differences in hippocampal (HIP) microglial activation and gene expression response were also evaluated.

resultsDMF treatment during stress exposure had antidepressant effects in male but not female rats, with no anxiolytic effects in either sex. Recognition learning and memory and spatial learning and memory were impaired in chronically stressed males and females, respectively, and DMF treatment rescued these deficits. DMF treatment also prevented stress-induced HIP microglial activation in males. Conversely, females displayed no HIP microglial activation associated with stress exposure. Last, chronic stress elicited sex-specific alterations in HIP gene expression, many of which were normalized in animals treated with DMF. Of note, most of the differentially expressed genes in males normalized by DMF were related to antioxidant, inflammatory or immune responses.

conclusionsCollectively, these findings support a greater role of immune processes in males than females in a rodent model of depression. This suggests that pharmacotherapies that target Nrf2 have the potential to be an effective sex-specific treatment for depression.

Indexed as

DepressionMajor Depressive DisorderAnimalsAntidepressive AgentsAntioxidantsDimethyl FumarateFemaleMaleNF-E2-Related Factor 2RatsAntidepressive AgentsAntioxidantsDimethyl FumarateNfe2l2 protein, ratNF-E2-Related Factor 2Dimethyl fumarateMajor depressive disorderNeuroinflammationNuclear factor erythroid 2-related factor 2Sex differences

Identifiers

PMID38350966
PMCPMC10863247
OpenAlexW4391786419

What OpenQuestion holds

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LicenceCC BY
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.