Psychopharmacology · 2025
Ketamine attenuates anxiety-like behavior and oxidative imbalance in the maternal immune activation model: emphasis on the cerebellum.
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de Oliveira Elifrances Galdino, de Souza Barbosa Mayara Victória, de Lima Diógenes Afonso, da Silva Júnior José Carlos, de Andrade Silva Severina Cassia, de Santana Jonata Henrique, Dos Santos Júnior Osmar Henrique, Lira Eduardo Carvalho, Lagranha Claudia J, Duarte Filipe Silveira, Gomes Dayane Aparecida
Аннотация
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.
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.