Evidence map›Paper›PMID 37968722›Full record

ArticleMolecular autism2023

Hyperthermia elevates brain temperature and improves behavioural signs in animal models of autism spectrum disorder.

Ana Belen Lopez-Rodriguez, Carol L Murray, John Kealy, Clodagh Towns, Andrew Roche, Arshed Nazmi, Michelle Doran, John P Lowry, Colm Cunningham

Abstract read
In one paragraph

Article in Molecular autism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
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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.

Ana Belen Lopez-RodriguezSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Republic of Ireland.
Carol L MurraySchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Republic of Ireland.
John KealySchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Republic of Ireland.
Clodagh TownsSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Republic of Ireland.
Andrew RocheSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Republic of Ireland.
Arshed NazmiSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Republic of Ireland.
Michelle DoranDepartment of Chemistry, Maynooth University, Maynooth, Co. Kildare, Republic of Ireland.
John P LowryDepartment of Chemistry, Maynooth University, Maynooth, Co. Kildare, Republic of Ireland.
Colm CunninghamSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Republic of Ireland. colm.cunningham@tcd.ie.

Funding

Simons Foundation SFARI 422623
6 · The paper itself

Abstract

backgroundAutism spectrum disorders (ASD) are predominantly neurodevelopmental and largely genetically determined. However, there are human data supporting the idea that fever can improve symptoms in some individuals, but those data are limited and there are almost no data to support this from animal models. We aimed to test the hypothesis that elevated body temperature would improve function in two animal models of ASD.

methodsWe used a 4 h whole-body hyperthermia (WBH) protocol and, separately, systemic inflammation induced by bacterial endotoxin (LPS) at 250 µg/kg, to dissociate temperature and inflammatory elements of fever in two ASD animal models: C58/J and Shank3B- mice. We used one- or two-way ANOVA and t-tests with normally distributed data and Kruskal-Wallis or Mann-Whitney with nonparametric data. Post hoc comparisons were made with a level of significance set at p < 0.05. For correlation analyses, data were adjusted by a linear regression model.

resultsOnly LPS induced inflammatory signatures in the brain while only WBH produced fever-range hyperthermia. WBH reduced repetitive behaviours and improved social interaction in C58/J mice and significantly reduced compulsive grooming in Shank3B- mice. LPS significantly suppressed most activities over 5-48 h. LIMITATIONS: We show behavioural, cellular and molecular changes, but provide no specific mechanistic explanation for the observed behavioural improvements.

conclusionsThe data are the first, to our knowledge, to demonstrate that elevated body temperature can improve behavioural signs in 2 distinct ASD models. Given the developmental nature of ASD, evidence that symptoms may be improved by environmental perturbations indicates possibilities for improving function in these individuals. Since experimental hyperthermia in patients would carry significant risks, it is now essential to pursue molecular mechanisms through which hyperthermia might bring about the observed benefits.

Indexed as

Autism Spectrum DisorderHyperthermia, InducedAnimalsBrainDisease Models, AnimalHumansLipopolysaccharidesMiceMice, Inbred StrainsTemperatureLipopolysaccharides

Identifiers

PMID37968722
PMCPMC10652497

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Registered trials

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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 OpenQuestion graph.