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Evaluation of metabolism-related molecules in rat model of autism spectrum disorders.

Experimental physiology2026

Tunçak Süeda, Çakır Ayşen, Gören Bülent, Kahveci Nevzat

What this study means for families

Scientists gave pregnant rats a medication called valproic acid and studied their babies to understand autism better. The baby rats showed autism-like behaviours including social difficulties and movement problems. Male and female rats were affected differently - males had higher blood sugar levels while females showed different anxiety patterns. The study found that certain brain chemicals related to appetite and metabolism changed in different ways between males and females, showing that autism may affect boys and girls differently.

Summary by AutismInsights from published abstract. This is not a substitute for reading the original paper.

Research summary

This preclinical study examined autism-like behaviours and metabolic changes in male and female rats exposed to valproic acid (VPA) before birth. VPA-exposed pups of both sexes showed impaired social behaviour, reduced movement, and delayed maternal recognition. Sex-specific differences emerged in anxiety responses and metabolic markers. Males showed elevated blood glucose levels, while females did not.

Brain and blood levels of metabolism-related molecules (leptin, nesfatin-1, orexin-A, ghrelin) were altered differently between sexes. The research demonstrates that prenatal VPA exposure creates autism-like symptoms with distinct sex-dependent metabolic and behavioural patterns, emphasising the importance of studying both males and females in autism research.

Summary by AutismInsights from published abstract. This is not a substitute for reading the original paper.

Key findings

  • 1

    VPA exposure caused autism-like behaviours in both sexes including reduced sociability and altered locomotion

    Confidence: moderateRelevance: Validates VPA animal model for studying autism spectrum behaviours across sexes
  • 2

    Sex-specific metabolic differences: elevated blood glucose in VPA-exposed males but not females

    Confidence: moderateRelevance: Suggests metabolic monitoring may be particularly important for males with autism
  • 3

    Altered levels of metabolism-related molecules (leptin, nesfatin-1, orexin-A, ghrelin) with sex-dependent patterns

    Confidence: moderateRelevance: Indicates potential biomarkers and therapeutic targets that may differ between sexes

Summary by AutismInsights from published abstract. This is not a substitute for reading the original paper.

Clinical implications

Findings suggest sex-specific metabolic monitoring and interventions may be needed in autism care. Research supports including both sexes in autism studies. Metabolism-related molecules may serve as potential biomarkers or therapeutic targets, but human validation studies are needed before clinical application.

Summary by AutismInsights from published abstract. This is not a substitute for reading the original paper.

Limitations

Animal model findings may not directly translate to humans. Sample size not reported, limiting statistical power assessment. Single time point measurement may miss developmental changes. VPA model represents only one potential pathway to autism-like behaviours.

Summary by AutismInsights from published abstract. This is not a substitute for reading the original paper.

Original abstract

Autism spectrum disorders (ASD) are neurodevelopmental pathologies. Investigating both sexes is crucial for understanding sex-specific manifestations of ASD. This study aims to examine ASD-like behaviours and metabolic alterations in male and female rats prenatally exposed to valproic acid (VPA). Pregnant Wistar albino rats were administered 400 mg/kg VPA or saline on embryonic day 12.

Pups were subjected to various behavioural tests, including olfactory discrimination, sociability, locomotion, anxiety and exploratory behaviour assessments. On postnatal day 35, pups were sacrificed, and blood glucose levels were measured. Serum and brain leptin, orexin-A, nesfatin-1 and ghrelin levels were assessed by the ELISA method. VPA-exposed pups exhibited increased latency to reach maternal bedding, reduced sociability, decreased locomotion and increased immobility in both sexes.

In the elevated plus maze, VPA-exposed females showed an increase in open-arm entries, while males showed a reduction compared to control groups. Blood glucose levels were significantly elevated in VPA-exposed males but not females. Significant sex-independent changes were observed in serum and brain levels of leptin and nesfatin-1 in the VPA groups. Brain orexin-A and serum ghrelin levels were altered in the VPA group in a sex-dependent manner.

Prenatal VPA exposure induces ASD-like symptoms in both sexes, with notable sex-specific differences in behaviour and metabolic regulation. These findings highlight the importance of including both sexes in ASD research to better understand sex-dependent characteristics of the disorder, particularly concerning metabolic dysregulation.

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Evidence Grade

Emerging

limited

Grade assigned by AutismInsights based on study type and published abstract.

Study Details

Journal
Experimental physiology
Year
2026
PMID
40930123
DOI
10.1113/EP092734

MeSH Terms

AnimalsFemaleMaleAutism Spectrum DisorderRats, WistarRatsPregnancyNucleobindinsPrenatal Exposure Delayed EffectsDisease Models, AnimalLeptinValproic AcidOrexinsBrainGhrelinBlood GlucoseBehavior, AnimalCalcium-Binding Proteins