Evidence map›Paper›PMID 40928517›Full record

ArticlePsychopharmacology2026

Alteration in hippocampal mitochondria ultrastructure and cholesterol accumulation linked to mitochondrial dysfunction in the valproic acid rat model of autism spectrum disorders.

Paula D Prince, Martín G Codagnone, Javier A W Opezzo, Juan S Adán Areán, Christian Höcht, Nathalie Arnal, Silvia Alvarez, Sandra Zárate, Analía Reinés

Abstract read
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In one paragraph

Article in Psychopharmacology, 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

9 authors.

Paula D PrinceInstituto de Biología Celular y Neurociencias "Prof. De Robertis" (IBCN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina.
Martín G CodagnoneInstituto de Biología Celular y Neurociencias "Prof. De Robertis" (IBCN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina.
Javier A W OpezzoFacultad de Farmacia y Bioquímica, Departamento de Farmacología, Farmacología, Universidad de Buenos Aires, Buenos Aires, Argentina.
Juan S Adán AreánFacultad de Farmacia y Bioquímica, Departamento de Ciencias Químicas, Fisicoquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Christian HöchtFacultad de Farmacia y Bioquímica, Departamento de Farmacología, Farmacología, Universidad de Buenos Aires, Buenos Aires, Argentina.
Nathalie ArnalInstituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CONICET- Universidad Nacional de La Plata, La Plata, Argentina.
Silvia AlvarezFacultad de Farmacia y Bioquímica, Departamento de Ciencias Químicas, Fisicoquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Sandra ZárateInstituto de Investigaciones Biomédicas (INBIOMED), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina.
Analía ReinésInstituto de Biología Celular y Neurociencias "Prof. De Robertis" (IBCN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina. areines@ffyb.uba.ar.ORCID http://orcid.org/0000-0002-7453-2224

Funding

Agencia Nacional de Promoción Científica y Tecnológica PICT-2018-2504Agencia Nacional de Promoción Científica y Tecnológica PICT-2020-2281Consejo Nacional de Investigaciones Científicas y Técnicas PIP 11220200101817COUniversidad de Buenos Aires UBACYT 20020170100478BAUniversidad de Buenos Aires UBACYT 20020220200135BA
6 · The paper itself

Abstract

rationaleAutism spectrum disorders (ASD) are a group of neurodevelopmental and multifactorial conditions with cognitive manifestations. The valproic acid (VPA) rat model is a well-validated model that successfully reproduces the behavioral and neuroanatomical alterations of ASD. Previous studies found atypical brain connectivity and metabolic patterns in VPA animals: local glucose hypermetabolism in the prefrontal cortex, with no metabolic changes in the hippocampus.

aimThis study aimed to explore mitochondrial structural features, lipid content, and functionality in the hippocampus and cerebral cortex in the VPA model.

methodsOn embryonic day 10.5, pregnant Wistar rats were injected with VPA (450 mg/kg) or saline solution. In the hippocampus and cerebral cortex of male offspring (postnatal day 35), the mitochondrial structure was evaluated by transmission electron microscopy, oxidized/reduced glutathione was determined by high-performance liquid chromatography, mitochondrial membrane cholesterol, and phospholipids were determined by thin-layer chromatography, and oxygen consumption and ATP synthesis were measured in isolated mitochondria.

resultsMitochondrial increased oxygen consumption and decreased ATP production, increased oxidized/reduced glutathione, cholesterol accumulation in mitochondrial membrane and altered mitochondrial structure were found in the hippocampus of VPA animals. All parameters were preserved in the cerebral cortex of VPA rats.

conclusionsThese findings reveal brain region-specific mitochondrial structural and functional alterations in VPA-treated animals, with preserved mitochondria in regions with high glucose demand and impaired mitochondria in metabolically normal areas. Moreover, cholesterol accumulation in hippocampal mitochondrial membranes is a potential cause of mitochondrial dysfunction, contributing to a prooxidant state.

Indexed as

Autism Spectrum DisorderCholesterolHippocampusMitochondriaValproic AcidAdenosine TriphosphateAnimalsCerebral CortexDisease Models, AnimalFemaleGlutathioneMaleOxygen ConsumptionPregnancyRatsRats, WistarAdenosine TriphosphateCholesterolGlutathioneValproic AcidAutism spectrum disordersBrain connectivityHippocampusMitochondriaMitochondrial lipid profilePrefrontal cortexValproic acid

Identifiers

PMID40928517

What Socratic holds

Textmetadata
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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 Socratic graph.