Proline reduces acetylcholinesterase activity in cerebral cortex of rats

Metab Brain Dis. 2003 Mar;18(1):79-86. doi: 10.1023/a:1021934803724.


In the present study we investigated the in vivo and in vitro effect of proline (Pro) on acetylcholinesterase (AChE) activity in rat cerebral cortex. The action of vitamins E and C on the effects produced by Pro was also tested. Twelve-day-old rats received one s.c. injection of Pro (12.8 micromol/g body weight) or an equivalent volume of 0.9% saline solution (control) and were killed 1 h later. In another set of experiments, 5-day-old rats were pretreated for 1 week with daily i.p. administration of saline (control) or vitamins E (40 mg/kg) and C (100 mg/kg). Twelve hours after the last injection the rats received one s.c. injection of Pro (12.8 micromol/g body weight) or saline (control) and were killed 1 h later. For the in vitro studies, cerebral cortex homogenates of 12-day-old untreated rats were incubated for 1 h with various concentrations of Pro (3.0 microM-1.0 mM) or with 1.0 mM Pro, 1.0 mM trolox, or 1.0 mM Pro plus 1.0 mM trolox. Controls did not contain Pro in the incubation medium. Our results showed that the AChE activity significantly decreased (25%) in rat brain subjected to Pro administration and that the pretreatment with vitamins E and C prevented this effect. Furthermore, Pro (0.5 and 1.0 mM) also inhibits AChE activity in vitro and trolox prevented this effect. The data suggest that the inhibitory effect of Pro on AChE activity is associated with oxidative stress. Although it is difficult to extrapolate our findings to the human condition, our results may be relevant to explain, at least in part, the neurologic dysfunction associated with hyperprolinemia type II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Antioxidants / pharmacology
  • Ascorbic Acid / pharmacology
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / enzymology*
  • Proline / antagonists & inhibitors
  • Proline / pharmacology*
  • Rats
  • Rats, Wistar
  • Vitamin E / pharmacology


  • Antioxidants
  • Vitamin E
  • Proline
  • Acetylcholinesterase
  • Ascorbic Acid