Systemic cisplatin exposure during infancy and adolescence causes impaired cognitive function in adulthood

Area of Science:

• Neuroscience
• Pediatric Oncology
• Cognitive Psychology

Background:

• Childhood cancer survivors face risks of chemotherapy-related cognitive impairments (CRCI).
• Methotrexate is linked to cognitive deficits in leukemia survivors; cisplatin's neurotoxicity in pediatric patients is understudied.
• Cisplatin crosses the blood-brain barrier, damages the hippocampus, and affects neural stem cells, posing a risk for cognitive impairment.

Purpose of the Study:

• To investigate the long-term cognitive effects of systemic cisplatin exposure during infancy and adolescence in a rat model.
• To compare the severity of cognitive dysfunction resulting from cisplatin treatment at different developmental stages.

Main Methods:

• Adult rats received systemic cisplatin during either infancy or adolescence.
• Cognitive function was assessed using behavioral tests, including novel object recognition, contextual discrimination, and cued fear conditioning.
• Control groups received no cisplatin treatment.

Main Results:

• Cisplatin administration during adolescence significantly impaired novel object retrieval compared to controls.
• Both infant and adolescent cisplatin exposure led to poor contextual discrimination and impaired cued fear conditioning.
• Adolescent cisplatin exposure resulted in more severe cognitive impairments than infant exposure, affecting hippocampus and amygdala-dependent functions.

Conclusions:

• Systemic cisplatin exposure during development causes long-lasting cognitive deficits.
• Adolescent exposure to cisplatin leads to more profound and global cognitive dysfunction than infant exposure.
• Pediatric cancer patients treated with cisplatin, particularly during adolescence, may be at high risk for long-term cognitive impairments.