Ketamine attenuates anxiety-like behavior and oxidative imbalance in the maternal immune activation model: emphasis on the cerebellum.
Elifrances Galdino de Oliveira, Mayara Victória De Souza Barbosa, Diógenes Afonso De Lima, José Carlos Da Silva Júnior, Severina Cassia De Andrade Silva, Jonata Henrique De Santana, Osmar Henrique Dos Santos Júnior, Eduardo Carvalho Lira, Claudia J Lagranha, Filipe Silveira Duarte, Dayane Aparecida Gomes
Psychopharmacology November 28, 2025 DOI: 10.1007/s00213-025-06974-w (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Male Swiss mouse offspring exposed prenatally to maternal immune activation via maternal lipopolysaccharide injection |
| Intervention | Ketamine |
| Dose | LPS 100 µg/kg/day; ketamine 20 mg/kg/day; saline 10 mL/kg/day |
| Duration | LPS on gestation days 15 and 16; ketamine from postnatal day 36 to 50; assessment on postnatal day 62 |
| Topics | Anxiety Ketamine Esketamine |
| Keywords | Cerebellum Maternal immune activation Oxidative imbalance |
| Key findings | Maternal immune activation increased anxiety-like behavior in male offspring, accompanied by elevated cerebellar TNF-α expression and oxidative imbalance. Ketamine treatment reversed the anxiety-like behavior and attenuated both the TNF-α increase and oxidative imbalance, suggesting the cerebellum is a site of lasting MIA-induced changes and a target of ketamine's effects. |
Abstract
Relevant to the study of neurodevelopmental disorders, maternal immune activation (MIA) models reproduce the high incidence of anxiety disorders and molecular alterations in the cerebellum reported in patients with schizophrenia and autism. In parallel, ketamine, a fast-acting antidepressant, has shown beneficial effects in psychiatric disorders with immune-related components. To investigate anxiety-like behavior, inflammatory status, and oxidative balance in the cerebellum of offspring exposed to MIA and to test the potential effects of ketamine postnatal treatment in reversing the behavior and molecular changes. To induce MIA, pregnant Swiss mice were intraperitoneally (i.p.) injected with lipopolysaccharide (LPS; 100 µg/kg/day) or saline (10 mL/kg/day) on gestation days 15 and 16, and subsequently, male offspring were administered saline (10 mL/kg/day) or ketamine (20 mg/kg/day) from postnatal day 36 to 50. On postnatal day 62, the offspring were assessed for anxiety-like behavior, and the cerebellum was collected for analysis of IL-1β, IL-6, TGF-β, and TNF-α gene expression and oxidative balance. Our results demonstrated that MIA increased anxiety-like behavior in offspring, accompanied by an increase in TNF-α expression, and oxidative imbalance in the cerebellum. Ketamine administration reversed the anxiety-like behavior, as well as attenuated both TNF-α expression and oxidative imbalance. Our findings suggest that the cerebellum is an important site of long-lasting changes induced by MIA and a relevant target of ketamine's effects. These results highlight the cerebellum's role in pathophysiological processes and its potential as a site for therapeutic intervention in psychiatric disorders.