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Related Experiment Videos

Hippocampal brain amines in methotrexate-induced learning and memory deficit.

Sampath Madhyastha1, S N Somayaji, M S Rao

  • 1Department of Anatomy, Kasturba Medical College, Manipal, Karnataka 576 119, India.

Canadian Journal of Physiology and Pharmacology
|December 20, 2002
PubMed
Summary

Intrathecal methotrexate causes learning and memory impairment in rats by reducing brain amines and damaging the hippocampus. This chemotherapy side effect may impact cognitive function in children with leukemia.

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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.

Related Experiment Videos

  • 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.