Hippocampal brain amines in methotrexate-induced learning and memory deficit

Area of Science:

• Neuroscience
• Pharmacology
• Oncology

Background:

• Intrathecal methotrexate (IT-MTX) is a chemotherapy agent used for leukemia.
• IT-MTX can cause neurological side effects, including cognitive dysfunction, in children.
• The precise mechanisms underlying methotrexate-induced neurotoxicity require further investigation.

Purpose of the Study:

• To investigate the cognitive and behavioral effects of methotrexate administration.
• To examine the impact of methotrexate on brain amine levels and hippocampal histology.
• To elucidate the neurobiological basis of methotrexate-induced cognitive dysfunction.

Main Methods:

• Male Wistar rats received multiple intracerebroventricular injections of methotrexate.
• Behavioral tests included the two-compartment conditioned avoidance task and dark-bright arena test.
• Brain amine levels were measured using HPLC, and hippocampal histopathology was assessed via cresyl violet staining.

Main Results:

• Methotrexate administration induced convulsions and impaired learning and memory.
• A significant reduction in norepinephrine, dopamine, serotonin, and 5-hydroxyindoleacetic acid levels was observed.
• Severe histopathological changes were noted in the CA4 region of the hippocampus.

Conclusions:

• Methotrexate disrupts brain monoamine concentrations and causes hippocampal damage, contributing to cognitive dysfunction.
• Cytotoxic effects of methotrexate on brain tissue are implicated in chemotherapy-induced brain dysfunction.
• Findings may inform therapeutic strategies for managing neurological side effects in pediatric leukemia patients.