Association of Neutrophil Elastase Activity, Oxidative Stress, Energy and Glutamate Metabolism Parameters with Behavior and Learning in Wistar Rats in a Postnatal Valproate Model of Autism Spectrum Disorder

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Anna A. Stakhanova^1,a*, Olga G. Voskresenskaya², Olga K. Savushkina¹, Tatyana A. Prokhorova¹, Elena B. Tereshkina¹, Ekaterina V. Semina¹, Svetlana A. Zozulya¹, Natalia V. Kost¹, and Yulia A. Chaika¹

¹Federal State Budgetary Scientific Institution, Russian Mental Health Research Center, 115522 Moscow, Russia

²Lomonosov Moscow State University, 119234 Moscow, Russia

^* To whom correspondence should be addressed.

Received: January 26, 2026; Revised: June 17, 2026; Accepted: June 19, 2026

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To study biochemical mechanisms underlying the development of autism spectrum disorders (ASD), an experimental model based on early postnatal administration of valproic acid (VPA) to Wistar rats was used. Social behavior impairments characteristic of ASD was accompanied by cognitive impairments and were associated with the increased neutrophil elastase (NE) activity in the serum and cerebellum of the rats treated with VPA. Increased NE activity in the cerebellum may indicate development of neuroinflammation. Impaired antioxidant defense under the influence of VPA was manifested by the increased glutathione S-transferase (GST) activity in the serum and cerebellum of rats. Correlation analysis revealed a link between the NE activity and formation of social behavior in animals. Enzymes of glutamate metabolism (glutamate dehydrogenase and glutamine synthetase) and antioxidant defense enzymes that regulate oxidative stress (OS) levels correlated with formation and maintenance of the acquired skills in both control and experimental animals.

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KEY WORDS: postnatal valproate model of autism spectrum disorders, rats, social behavior, memory, neuroinflammation, neutrophil elastase, oxidative stress, energy metabolism, glutamate metabolism, glutathione S-transferase, creatine phosphokinase, cerebellum

DOI: 10.1134/S0006297926600158

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