The effects of chemotherapy on cognitive function in a mouse model: a prospective study

Area of Science:

• Neuroscience
• Pharmacology
• Oncology

Background:

• Chemotherapy is associated with cognitive impairment in up to 70% of cancer patients.
• The precise neurological mechanisms and long-term cognitive effects of chemotherapy remain incompletely understood.

Purpose of the Study:

• To investigate the short- and long-term effects of common chemotherapeutic agents on cognitive performance.
• To utilize a prospective longitudinal mouse model to assess chemotherapy-induced cognitive deficits.

Main Methods:

• Mice received weekly injections of methotrexate + 5-fluorouracil (CHEMO) or saline (control).
• Cognitive tests assessing learning and memory were administered pre-treatment, post-treatment, and three months later.
• Structural MRI scans were performed concurrently with cognitive testing.

Main Results:

• Chemotherapy treatment led to significant deficits in pre-existing knowledge (spatial memory, NMTS learning) and new learning (associative and discrimination learning).
• Cognitive impairments were particularly evident in tasks sensitive to hippocampal and frontal lobe function, suggesting broader neurological impact.
• Deficits persisted for at least three months post-treatment, with partial recovery observed in tasks related to frontal lobe control.

Conclusions:

• Chemotherapeutic agents adversely affect both previously acquired information and new learning and memory.
• Cognitive impairment resulting from chemotherapy is long-lasting, even with partial recovery observed over time.