Evidence map›Paper›PMID 41504877›Full record

ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2026

Cumulative environmental exposures adversely impact social behaviour and are associated with dysregulation of genes and proteins involved in epigenetic, ribosomal, and immune regulation in male mice.

Morgan C Bucknor, Brooke A Keating, Velda X Han, Brian S Gloss, Pinki Dey, Nader Aryamanesh, Lee L Marshall, Mark E Graham, Ruwani Dissanayake, Xianzhong Lau and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 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. Medicinal cannabis plant extract (NTI164) modifies epigenetic, ribosomal, and immune pathways in paediatric acute-onset neuropsychiatric syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Trial
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

16 authors.

Morgan C BucknorSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.
Brooke A KeatingKids Neuroscience Centre, Faculty of Medicine and Health, The Children's Hospital at Westmead, University of Sydney, Sydney, NSW, Australia.
Velda X HanDivision of Paediatric Neurology, Department of Paediatrics, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, Singapore, Singapore.
Brian S GlossWestmead Research Hub, Westmead Institute for Medical Research, Westmead, Sydney, NSW, Australia.
Pinki DeyBioinformatics Group, Children's Medical Research Institute, University of Sydney, Sydney, NSW, Australia.
Nader AryamaneshBioinformatics Group, Children's Medical Research Institute, University of Sydney, Sydney, NSW, Australia.
Lee L MarshallBioinformatics Group, Children's Medical Research Institute, University of Sydney, Sydney, NSW, Australia.
Mark E GrahamBiomedical Proteomics, Children's Medical Research Institute, University of Sydney, Sydney, NSW, Australia.
Ruwani DissanayakeAustralian Genome Research Facility Ltd, Westmead, NSW, Australia.
Xianzhong LauAustralian Genome Research Facility Ltd, Melbourne, VIC, Australia.
Shrujna PatelKids Neuroscience Centre, Faculty of Medicine and Health, The Children's Hospital at Westmead, University of Sydney, Sydney, NSW, Australia.
Stela P PetkovaThe Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia.
Peter ValtchevSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.
Anand GururajanChildren's Medical Research Institute, University of Sydney, Sydney, NSW, Australia.
Russell C DaleKids Neuroscience Centre, Faculty of Medicine and Health, The Children's Hospital at Westmead, University of Sydney, Sydney, NSW, Australia.
Markus J HoferSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia. markus.hofer@sydney.edu.au.

Funding

National Health and Medical Research Council APP1193648
6 · The paper itself

Abstract

objectiveThis study investigated how cumulative environmental exposures influence offspring behaviour and inflammation-related molecular signatures in the brain and peripheral immune system.

methodsA novel "triple-hit" mouse model was developed using C57Bl/6JAusB mice (N = 70), combining preconceptual social stress, antenatal high-fat diet, and a postnatal immune challenge (poly(I:C), 10 mg/kg). At 12 weeks, offspring underwent behavioural tests relevant to neurodevelopmental disorders (NDDs), including the Elevated Plus Maze, 3-Chamber Social Preference, Self-Grooming, and Marble Burying. A composite NDD-risk index was calculated. Single-cell RNA sequencing (scRNA-seq) and bulk proteomics were performed on male triple-hit offspring to identify differentially expressed genes and proteins associated with inflammatory pathways.

resultsMale triple-hit offspring showed elevated NDD-related behavioural risk and social deficits, not observed in females. scRNA-seq revealed altered inflammatory and ribosomal pathways in brain glia and peripheral immune cells. Proteomic analysis showed decreased abundance of proteins involved in inflammation, translation, chromatin remodelling, and synaptic function in both brain and blood.

conclusionCombined environmental stressors may drive male-specific behavioural and inflammatory changes relevant to NDDs. The identification of overlapping inflammatory signatures in brain and peripheral immune cells supports a role for shared immune mechanisms in brain-immune axis dysfunction. However, these pathway-level findings should be interpreted as preliminary hypotheses and warrant independent validation to confirm their mechanistic significance.

Indexed as

Environmental ExposureNeurodevelopmental DisordersPrenatal Exposure Delayed EffectsSocial BehaviorStress, PsychologicalAnimalsBehavior, AnimalBrainDiet, High-FatEpigenesis, GeneticFemaleInflammationMaleMiceMice, Inbred C57BLPoly I-CPoly I-CEnvironmental stressHigh-fat dietImmuneInflammationNeurodevelopmental disordersPoly(I:C)

Identifiers

PMID41504877
PMCPMC12783315

What OpenQuestion holds

Textmetadata
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.