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Rationale <p>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.</p> Objectives <p>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.</p> Methods <p>To induce MIA, pregnant Swiss mice were intraperitoneally (i.p.) injected with lipopolysaccharide (LPS; 100&#xa0;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&#xa0;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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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Ketamine attenuates anxiety-like behavior and oxidative imbalance in the maternal immune activation model: emphasis on the cerebellum

  • 期刊论文

  • 发表日期：

    2025年11月28日

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  • 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

摘要

Rationale

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.

Objectives

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.

Methods

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.

Results

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.

Conclusions

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.