Long-term neurobehavioral and histological damage in brain of mice induced by L-cysteine

Vered Gazit, Ron Ben-Abraham, Chaim G. Pick, Izhar Ben-Shlomo, Yeshayahu Katz

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


We investigated whether structural central neural damage and long-term neurobehavioral deficits after L-cysteine (L-Cys) administration in mice is caused by hypoglycemia. Neonatal ICR mice were injected subcutaneously with L-Cys (0.5-1.5 mg/g body weight [BW]) or saline (control). Blood glucose was measured. At 50 days of age, mice were introduced individually into an eight-arm maze for evaluation of spatial memory (hippocampal-related behavior). Times for visiting all eight arms and number of entries until completion of the eight-arm visits (maze criteria) were measured. The test was repeated once daily for 5 days. In situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was used for detection of brain damage. As early as 20 min and up to 2 h postinjection, animals treated with L-Cys doses higher than 1.2 mg/g BW developed hypoglycemia and looked ill. Several animals convulsed. Long-term survivors required more time, in a dose-dependent manner, to assimilate the structure of the maze, and animals treated with L-Cys (1.5 mg/g BW) exhibited TUNEL-positive changes in the hippocampal regions. All these changes were reversible by coadministration of glucose. We conclude that L-Cys injection can cause pronounced hypoglycemia associated with long-term neurobehavioral changes and central neural damage in mice. Since L-Cys is chemically different from the other excitatory amino acids (glutamate and aspartate), the long-reported L-Cys-mediated neurotoxicity may be connected to its hypoglycemic effect.

Original languageEnglish
Pages (from-to)795-799
Number of pages5
JournalPharmacology Biochemistry and Behavior
Issue number4
StatePublished - Jul 2003
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by grants from the Bruce Rappaport Faculty of Medicine, the Technion VPR Fund, the Mitchell Family Foundation, the Soref Family Foundation (Y.K.), and the German–Israeli Foundation for Scientific Research and Development (I.B.-S.). We thank Miss Ruth Singer for skillful editing.


  • Behavior
  • Brain damage
  • Eight-arm maze
  • Neurotoxicity


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